Publications by authors named "Ziba Rahimi"

38 Publications

Variants of Genes Involved in Metabolism of Folate Among Patients with Breast Cancer: Association of 3R Allele with Susceptibility to Breast Cancer and Metastasis.

Iran J Pathol 2021 10;16(1):62-68. Epub 2020 Nov 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC.

Methods: The present case-control study includes 100 BC patients and 141 healthy females. The  2R/3R (rs34743033),  c.2756A>G (rs1805087), and c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively.

Results: The 3R allele of enhanced the risk of BC by 2.84-fold (<0.001). In the presence of 3R/3R, compared to 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, =0.055). The frequencies of c.2756A>G and c.66A>G variants were not significantly different among patients and controls.

Conclusion: We observed that the 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .
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http://dx.doi.org/10.30699/ijp.2020.117676.2283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691710PMC
November 2020

Gene variants and haplotypes of Vitamin D biosynthesis, transport, and function in preeclampsia.

Hypertens Pregnancy 2021 Feb 11;40(1):1-8. Epub 2020 Dec 11.

Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences , Kermanshah, Iran.

: To find whether the gene variants and haplotypes of cytochrome (CYP) 27B1 (1α-hydroxylase), group-specific component (GC) that is a vitamin D binding protein, vitamin D receptor (VDR), peroxisome proliferator-activated receptor γ (PPARγ) and retinoid-X receptor (RXR) affect the risk of preeclampsia. : In a case-control study 100 women with preeclampsia and 100 healthy pregnant women were investigated for gene variants and haplotypes of vitamin D biosynthesis, transport, and function using the polymerase chain reaction-restriction fragment length polymorphism method. : The frequency of gene variants of PPARγ Pro12Ala and RXR -α (A/G, rs749759) were not significantly different comparing patients and controls. The TT genotype of CYP 27B1 (G > T) was associated with 2.2-fold (95% CI 1.04-4.7, p = 0.039) increased risk of early-onset preeclampsia. Also, the TT genotype of GC rs7041 (T > G) increased the risk of preeclampsia [OR = 2.13 (95% CI 1.09-4.17, p = 0.027)]. The VDR ApaI GT genotype elevated susceptibility to preeclampsia (OR = 2.55, p = 0.04). Further, the presence of VDR ApaI GT+TT genotype was associated with higher levels of body mass index, and systolic blood pressure, and lower level of 25 (OH)-D3. In the presence of haplotype CYP T, VDR T, and RXR A (TTA) compared to haplotype GTG the risk of preeclampsia was 6.71-fold (p = 0.044). : The present study indicated an association between the CYP 27B1, GC, and VDR ApaI variants with the risk of preeclampsia. Also, the variants of the latter polymorphism influenced BMI, blood pressure, and vitamin D levels.
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http://dx.doi.org/10.1080/10641955.2020.1849274DOI Listing
February 2021

Association between CYP19A

Int J Mol Cell Med 2019 20;8(2):162-168. Epub 2019 Jul 20.

Department of Internal Medicine, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A
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http://dx.doi.org/10.22088/IJMCM.BUMS.8.2.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081083PMC
July 2019

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with .

Iran J Pathol 2020 ;15(1):23-29

Department of Internal Medicine, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background & Objective: To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV).

Methods: In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively.

Results: The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele.

Conclusion: We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.
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http://dx.doi.org/10.30699/IJP.2019.105695.2098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995677PMC
January 2020

The Prevalence of Hemoglobinopathies in Reference Laboratory of Kermanshah, Western Iran.

Iran J Public Health 2019 Feb;48(2):359-361

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556188PMC
February 2019

NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia.

Oncol Lett 2019 Apr 19;17(4):4016-4023. Epub 2019 Feb 19.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 67148-69914, Iran.

Mutations in certain genes have been suggested to be associated with the pathogenesis of chronic lymphocytic leukemia (CLL), which is the most common leukemia in adults. In a case-control study, 100 patients with CLL and 105 healthy individuals were investigated for Notch homolog 1, translocation-associated () (NOTCH1) c.7544-7545delCT, recombinant splicing factor 3B subunit 1 (SF3B1) c.2098A>G, mouse double minute 2 homolog (MDM2) 40-bp insertion/deletion and myeloid differentiation primary response 88 (MYD88) L265P mutations by using allele specific-polymerase chain reaction (AS-PCR), a designed AS-PCR, PCR and PCR-restriction fragment length polymorphism methods, respectively. The presence of NOTCH1 and SF3B1 mutations were confirmed by genomic DNA sequencing. The NOTCH1 mutation was detected in 10% of patients and not detected in the control group. A higher frequency of NOTCH1 mutation was detected in patients with stage III CLL (62.5%) compared with stages 0-II CLL (37.5%) (odds ratio, 4.69-fold; 95% confidence interval, 1.0-21.9; P=0.049). The SF3B1 mutation was observed in 12% of the patients compared with 1.9% of the controls (P=0.012). The presence of MDM2 polymorphism was not associated with the risk or the stage of the disease. In addition, the MYD88 L265P mutation was not detected in the patients or the controls. The current study established the frequency of NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with CLL from the Kurdish population of Western Iran. In summary, a high frequency of NOTCH1 and SF3B1 mutations were identified in patients with CLL compared with healthy individuals, and the NOTCH1 mutation was associated with a high stage of the disease.
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http://dx.doi.org/10.3892/ol.2019.10048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425375PMC
April 2019

The effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index.

J Cell Biochem 2019 04 11;120(4):6441-6448. Epub 2018 Nov 11.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

We investigated the influence of vitamin D receptor (VDR) polymorphisms and vitamin D level on the blood pressure and the risk of preeclampsia. In a case-control study, 200 pregnant women, including 100 individuals with preeclampsia along with 100 healthy pregnant women, were studied for VDR FokI, TaqI, and BmsI polymorphisms and serum 25 (OH)-D level using polymerase chain reaction-restriction fragment length polymorphism method and commercial kit, respectively. The mean level of 25 (OH)-D in preeclamptic patients was significantly lower (16.6 ± 4.2 ng/mL, P < 0.001) compared with controls (19.6 ± 3.8 ng/mL). Among all women, a significantly higher systolic blood pressure and before-pregnancy body mass index and also lower gestational age were observed in the presence of 25 (OH)-D level < 20 ng/mL compared with the 20 to 30 ng/mL. A significantly higher frequency of VDR FokI C allele in preeclamptic patients (83%) than controls (74%) was associated with a 1.72-fold increased risk of preeclampsia. In all the studied individuals, the systolic and diastolic blood pressures were significantly higher in the presence of the FokI CC genotype compared with the TC and TT+TC genotypes. Neither VDR Taq1 nor VDR BmsI was associated with the risk of preeclampsia. The haplotype FokI C, TaqI C and BmsI A (CCA) compared with haplotype CTG increased the risk of preeclampsia by 1.4-fold (P = 0.33). Our study suggests an association between VDR FokI polymorphism and an insufficient serum level of 25 (OH)-D with the risk of preeclampsia and also the influence of insufficient 25 (OH)-D level and VDR FokI polymorphism on maternal factors, including blood pressure.
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http://dx.doi.org/10.1002/jcb.27934DOI Listing
April 2019

The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles.

Int J Fertil Steril 2018 Jul 18;12(2):147-151. Epub 2018 Mar 18.

Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR) γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS) and their influence on lipid and lipoprotein profiles of patients.

Materials And Methods: The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran). The PPARγ Pro12Ala and PPARγ C161T polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS), serum triglycerides (TG), cholesterol, low density lipoprotein- cholesterol (LDL-C), high density lipoproteincholesterol (HDL-C) and estradiol levels were measured.

Results: The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG) genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T) was 21% in patients and 17.2% in controls with no significant difference (P=0.52). In all studied individuals, the PPARγ CG genotype was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype.

Conclusion: Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.
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http://dx.doi.org/10.22074/ijfs.2018.5270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936613PMC
July 2018

PPARγ Pro12Ala and C161T polymorphisms in patients with acne vulgaris: Contribution to lipid and lipoprotein profile.

Adv Med Sci 2018 Mar 6;63(1):147-151. Epub 2017 Nov 6.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Purpose: The aim of present study was to clarify the role of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala and C161T variants in the pathogenesis of acne vulgaris (AV) and their influence on lipid and lipoprotein profile.

Methods: The present case-control study consisted of 393 individuals including 198 patients with AV (mild-, moderate-, and severe-AV) and 195 unrelated age-matched healthy individuals from Western Iran. The PPARγ Pro12Ala and C161T polymorphisms were identified using polymerase chain reaction-restriction length polymorphism method. Also, serum lipid and lipoprotein profile and fasting blood sugar (FBS) were detected in studied individuals.

Results: In women patients with AV significantly higher serum levels of FBS, total cholesterol, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol compared to healthy women were detected. Neither PPARγ Pro12Ala nor C161T polymorphism was associated with the risk of AV but the Pro allele was a risk factor for AV among all men and women patients ≥20years. The variant genotype of PPARγ CG (Pro/Ala) was associated with significantly higher levels of total cholesterol and triglycerides compared to CC (Pro/Pro) genotype. We detected a significantly lower level of FBS in the presence of CT+TT genotype of PPARγ C161T compared to CC genotype. Also, carriers of PPARγ TT genotype had significantly lower serum level of total cholesterol and LDL-C compared to CC genotype.

Conclusions: Our results demonstrated the association of PPARγ Pro allele with susceptibility to AV in patients ≥20years and the influence of PPARγ Pro12Ala and C161T polymorphisms on the lipid and lipoprotein profile.
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http://dx.doi.org/10.1016/j.advms.2017.09.003DOI Listing
March 2018

Matrix metalloproteinase-2 C-735T and its interaction with matrix metalloproteinase-7 A-181G polymorphism are associated with the risk of preeclampsia: influence on total antioxidant capacity and blood pressure.

J Obstet Gynaecol 2018 Apr 10;38(3):327-332. Epub 2017 Oct 10.

a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were studied in 144 pregnant patients with mild and severe preeclampsia and 103 healthy pregnant women. Significantly higher frequencies of CT and TT genotypes in patients compared to controls increased the risk of preeclampsia by 2.42 and 3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2 CT the level of total antioxidant capacity was significantly lower than MMP-2 CC genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly increased compared to CC genotype in all the patients. The combined presence of MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles significantly increased the risk of preeclampsia by 3.08-fold. Our findings demonstrate an association between the MMP-2 C-735 T polymorphism with blood pressure and the risk of preeclampsia. Also, in the presence of polymorphism total antioxidant capacity level decreased in severe preeclampsia. Impact statement What is already known on this subject: Matrix metalloproteinases (MMPs) including MMP-2 might be involved in the pathogenesis of preeclampsia through alteration of invasive ability of trophoblastic cells and abnormal placentation. In one available study the absence of association between MMP-2 C-735T polymorphism with gestational hypertension or preeclampsia has been reported. What the results of this study add: We found that the presence of MMP-2 C-735T polymorphism increased the risk of preeclampsia and there was a significantly lower level of total antioxidant capacity in the presence of the polymorphism in severe preeclampsia. Also, we found significantly higher systolic and diastolic blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of preeclampsia. What the implications are of these findings for clinical practice and/or further research: New findings of our study are involvement of lower activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter activity allele, in the pathogenesis of preeclampsia through possible impairment of placentation and also by decreased total antioxidant capacity and increased blood pressure. Further association studies of the role of MMP-2 polymorphism and MMP-2 activity in relation to oxidative stress parameters and blood pressure could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.
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http://dx.doi.org/10.1080/01443615.2017.1354178DOI Listing
April 2018

MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia: Association between MMP-8 C-799T with susceptibility to severe preeclampsia.

Clin Exp Hypertens 2018 26;40(2):175-178. Epub 2017 Jul 26.

a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Objective: The aim of present study was to determine the role of matrix metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052) polymorphisms in susceptibility to preeclampsia.

Study Design: In a case-control study, 256 pregnant women including 152 women with preeclampsia (86 women with mild preeclampsia and 66 women with severe preeclampsia) and 104 women with normal pregnancy from Western Iran with Kurdish ethnic background were investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method.

Results: Comparing the MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated a significantly higher frequency of the MMP-8 TT genotype (47%) in severe preeclamptic patients than that in healthy pregnant women (30.8%) that was associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05-3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic patients compared to 30.2% in controls (p = 0.56). Also, no significant difference was detected comparing the frequency of G allele in mild (26.6%, p = 0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%).

Conclusions: Our study demonstrated that the MMP-8 C-799T is associated with the risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C + 17G polymorphism might not be a risk factor for susceptibility to preeclampsia.
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http://dx.doi.org/10.1080/10641963.2017.1346115DOI Listing
June 2018

I/D and A-181G variants and the risk of end stage renal disease.

Mol Biol Res Commun 2017 Mar;6(1):41-44

Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

The variants of angiotensin converting enzyme () and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the insertion/deletion (I/D) and A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of I/D variants was not significantly different between ESRD patients and controls. However, the presence of D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for AG genotype in the pathogenesis of ESRD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396814PMC
March 2017

The T Allele of MTHFR c.C677T and Its Synergism with G (Val 158) Allele of COMT c.G472A Polymorphism Are Associated with the Risk of Bipolar I Disorder.

Genet Test Mol Biomarkers 2016 Sep 22;20(9):510-5. Epub 2016 Jul 22.

2 Medical Biology Research Center, Kermanshah University of Medical Sciences , Kermanshah, Iran .

Aims: The aims of the present study were to investigate the association between methylenetetrahydrofolate reductase (MTHFR) c.C677T (p.A222V) and catechol-O-methyltransferase (COMT) c.G472A (p.V158M) polymorphisms and their synergism with respect to bipolar I disorder (BID).

Methods: Within an ethnic Kurdish population from Western Iran the MTHFR c.C677T and COMT c.G472A polymorphisms were studied in 150 patients with BID and 149 gender- and age-matched healthy individuals using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: In the presence of MTHFR 677T allele and MTHFR TT genotype, the risk of BID was 1.44 times (p = 0.046) and 1.81-fold (p = 0.029), respectively. The frequency of COMT 472G allele compared to the A allele in cases and controls was not significant (p = 0.078); however there was a synergism between the presence of MTHFR 677T and COMT 472G alleles that increased the risk of BID by 2.58-fold (p = 0.003).

Conclusions: Our findings indicate that the presence of the lower activity allele of MTHFR (677T) increased the risk of BID. In addition, the concomitant presence of the MTHFR 677T allele with the COMT 472G allele was associated with increased susceptibility to BID in our population.
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http://dx.doi.org/10.1089/gtmb.2016.0061DOI Listing
September 2016

Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis.

Immunol Invest 2016 Aug 13;45(6):543-52. Epub 2016 Jul 13.

f Fertility and Infertility Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood-brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case-control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene-gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP-7, and MMP-9 genes might increase the risk of MS.
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http://dx.doi.org/10.1080/08820139.2016.1180303DOI Listing
August 2016

MMP-7 A-181G Polymorphism in Breast Cancer Patients from Western Iran.

Breast Care (Basel) 2015 Dec 15;10(6):398-402. Epub 2015 Dec 15.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Matrix metalloproteinases (MMPs) are upregulated in tumors. The MMP-7 A-181G polymorphism is associated with increased expression of the MMP-7 gene. Aim of the present study was to investigate the association between the MMP-7 A-181G polymorphism and susceptibility to breast cancer.

Patients And Methods: The MMP-7 A-181G variants were studied in a cohort of 251 subjects consisting of 100 breast cancer patients and 151 healthy controls; all were from Western Iran. The MMP-7 A-181G genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: The frequencies of the MMP-7 AA, AG, and GG genotypes in healthy individuals were 34.4, 50.4, and 15.2%, respectively. In breast cancer patients, the frequencies of AA (34%), AG (52%), and GG (14%) genotypes (p = 0.95) were similar to those in the controls. There was a trend toward an increased frequency of the combined genotype of MMP-7 AG+GG in patients with lymph node metastasis (70.4%) compared to those without metastasis (66.7%). Also, in patients with invasive lobular carcinoma, the frequency of the MMP-7 AG+GG genotype tended to be higher (71.4%) compared to that in patients with invasive ductal carcinoma (66.2%) (p = 0.78).

Conclusion: Our findings indicate that the MMP-7 A-181G polymorphism may not be correlated with susceptibility to breast cancer in our population.
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http://dx.doi.org/10.1159/000442231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789881PMC
December 2015

AT1R A1166C variants in patients with type 2 diabetes mellitus and diabetic nephropathy.

J Nephropathol 2015 Jul 1;4(3):69-76. Epub 2015 Jul 1.

Department of Nephrology, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: There are inconsistent reports related to the role of angiotensin II type 1 receptor (AT1R) on the risk of type 2 diabetes mellitus (T2DM) and its renal complications.

Objectives: To identify the association between AT1R A1166C variants with the risk of T2DM and also with diabetic nephropathy (DN).

Patients And Methods: In a case-control study, the AT1R A1166C polymorphism was detected in 135 T2DM patients with and without DN and in 98 healthy subjects from Western Iran. The genotypes of AT1R A1166C polymorphism were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: The frequencies of AT1R A1166C genotypes and alleles were not significantly difference between patients with and without DN and controls. The frequencies of rare allele of 1166 C were 10%, 16.5%, 15.9% and 15.3% in micro-, macro- and normo-albuminuric patients and in healthy individuals, respectively ( P > 0.05). The systolic blood pressure and serum creatinine level in DN patients were significantly higher in carriers of AT1R CC compared to carriers of AT1R AA genotype. In the presence of uncontrolled hyperglycemia (HbA1c > 7.5%), there was a trend toward increased risk of macro-albuminuria in carriers of AC+CC genotype (OR=3.66, [95% CI: 0.81-16.58], P = 0.092).

Conclusions: Our study indicated the absence of an association between AT1R A1166C polymorphism with the risk of T2DM and DN. It seems in carriers of AT1R C allele systolic blood pressure and serum creatinine level to be higher compared to the A allele carriers.
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http://dx.doi.org/10.12860/jnp.2015.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544557PMC
July 2015

Matrix metalloproteinase-9 -1562T allele and its combination with MMP-2 -735 C allele are risk factors for breast cancer.

Asian Pac J Cancer Prev 2015 ;16(3):1175-9

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran E-mail :

Background: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP- 2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background.

Materials And Methods: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02- 1.98, p=0.036)].

Conclusions: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.
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http://dx.doi.org/10.7314/apjcp.2015.16.3.1175DOI Listing
December 2015

Cancer notification at a referral hospital of Kermanshah, Western Iran (2006-2009).

Asian Pac J Cancer Prev 2015 ;16(1):133-7

Medical Biology Research Center, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran E-mail :

Background: Cancer is a major public health problem and the leading cause of mortality in both males and females in developed and developing countries. The incidence of cancer is gender dependent. Among Iranians, it is the third cause of death.

Materials And Methods: The information recorded in the files of all patients (7,695 individuals) pathologically diagnosed with cancer in Imam Reza referral hospital of Kermanshah University of Medical Sciences during the four year period of 2006-2009 were reviewed and analyzed using SPSS statistical software package version 16.0.

Results: Around 61.6% of reported cancer cases were males and 38.4% were females. The most prevalent reported malignant tumors occurred at the age group of 70-79 years in males and in females these tumors were presented in the ages of 60-69 years. The most prevalent cancers among studied patients were gastrointestinal (GI) cancers with a frequency of 22.9% [gastric 10.7%, colorectal 6.9%, and esophageal 6%]. The second, third and forth prevalent cancers were blood at 16.4%, lung 13.5% and bladder 12.8%, respectively. In males the cancers of GI (25.6%) were the most prevalent followed in order of frequency by bladder (18%), blood (17.6%), lung (17.4%) and prostate (6.8%) . In females the most frequent recorded cancer was breast (24.1%) followed in order of frequency by GI (20.5%), blood (14.4%), lung (7.3%), uterus (6.2%) and ovary (5.1%) . Breast cancer was the most prevalent cancer (27%) in the age group of 40-49 years.

Conclusions: The present study provides frequency data for various types of cancers in both males and females from a referral hospital of Kermanshah that are comparable with some reports from other areas of the country.
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http://dx.doi.org/10.7314/apjcp.2015.16.1.133DOI Listing
October 2015

Cancer notification at a referral hospital of Kermanshah, Western Iran (2006-2009).

Asian Pac J Cancer Prev 2015 ;16(1):133-7

Medical Biology Research Center, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran E-mail :

Background: Cancer is a major public health problem and the leading cause of mortality in both males and females in developed and developing countries. The incidence of cancer is gender dependent. Among Iranians, it is the third cause of death.

Materials And Methods: The information recorded in the files of all patients (7,695 individuals) pathologically diagnosed with cancer in Imam Reza referral hospital of Kermanshah University of Medical Sciences during the four year period of 2006-2009 were reviewed and analyzed using SPSS statistical software package version 16.0.

Results: Around 61.6% of reported cancer cases were males and 38.4% were females. The most prevalent reported malignant tumors occurred at the age group of 70-79 years in males and in females these tumors were presented in the ages of 60-69 years. The most prevalent cancers among studied patients were gastrointestinal (GI) cancers with a frequency of 22.9% [gastric 10.7%, colorectal 6.9%, and esophageal 6%]. The second, third and forth prevalent cancers were blood at 16.4%, lung 13.5% and bladder 12.8%, respectively. In males the cancers of GI (25.6%) were the most prevalent followed in order of frequency by bladder (18%), blood (17.6%), lung (17.4%) and prostate (6.8%) . In females the most frequent recorded cancer was breast (24.1%) followed in order of frequency by GI (20.5%), blood (14.4%), lung (7.3%), uterus (6.2%) and ovary (5.1%) . Breast cancer was the most prevalent cancer (27%) in the age group of 40-49 years.

Conclusions: The present study provides frequency data for various types of cancers in both males and females from a referral hospital of Kermanshah that are comparable with some reports from other areas of the country.
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http://dx.doi.org/10.7314/apjcp.2015.16.1.133DOI Listing
October 2015

Association of matrix metalloproteinase-7A-181G variants with the risk of multiple sclerosis.

Per Med 2014 Nov;11(8):727-733

Research Center for Environmental Determinants of Health, School of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Aim: To investigate the influence of matrix metalloproteinase-7 (MMP-7) A-181G on the risk of multiple sclerosis (MS) and neurological disability.

Patients & Methods: The variants of MMP-7 were studied in 126 MS patients and 190 healthy controls.

Results: The MMP-7 G allele and AG+GG genotype significantly increased the risk of MS in females (odds ratio: 1.59; p = 0.011) and patients with the age at disease onset of ≤19 years (odds ratio: 8.77; p = 0.038), respectively. Patients with clinical course of secondary progressive MS carriers of AG genotype had higher mean Expanded Disability Status Scale (4.9 ± 0.85; p = 0.01) compared with carriers of AA genotype (3.75 ± 0.41).

Conclusion: The MMP-7 A-181G polymorphism might be associated with susceptibility to MS in females and individuals with the age at disease onset of ≤19 years and with neurological disability in secondary progressive MS.
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http://dx.doi.org/10.2217/pme.14.42DOI Listing
November 2014

The MMP-2 -735 C allele is a risk factor for susceptibility to breast cancer.

Asian Pac J Cancer Prev 2014 ;15(15):6199-203

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran E-mail :

Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer.

Materials And Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients≤40 years (88.9%) than those aged ≥41 years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31).

Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.
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http://dx.doi.org/10.7314/apjcp.2014.15.15.6199DOI Listing
January 2017

Matrix metalloproteinase-7 A-181G and its interaction with matrix metalloproteinase-9 C-1562T polymorphism in preeclamptic patients: association with malondialdehyde level and severe preeclampsia.

Arch Gynecol Obstet 2015 Jan 26;291(1):45-51. Epub 2014 Jul 26.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box: 67148-69914, Kermanshah, Iran,

Purpose: The abnormal activation of matrix metalloproteinases (MMPs) during pregnancy might be involved in the pathogenesis of preeclampsia. The aim of present study was to investigate the possible influence of MMP-7 A-181G and its interaction with MMP-9 C- 1562T polymorphism on the risk of preeclampsia and lipid peroxidation level.

Methods: In a case-control study the MMP-7 A-181G and MMP-9 C-1562T polymorphisms were studied in 168 preeclamptic and 154 healthy pregnant women from Western Iran. The MMP-7 and-9 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism method.

Results: The frequency of MMP-7 G allele in mild- (37.4 %) and severe-preeclampsia (45.6 %) and controls (40.3 %) were not significantly different. In preeclamptic patients in the presence of MMP-7 AG + GG genotype there was a significantly higher concentration of malondialdehyde (MDA) (10.52 ± 4.18 μM, p = 0.017) compared to that in AA genotype carriers (9 ± 2.89 μM). Also, in the presence of both MMP-7 G and MMP-9 T alleles the MDA concentration (11.6 ± 4.9 μM) was significantly higher compared to the concomitant presence of MMP-7 A and MMP-9 C wild alleles (9.2 ± 3.1 μM, p = 0.02). There was an interaction between two alleles of MMP-7 G and MMP-9 T that significantly increased the risk of severe preeclampsia by 1.4-fold (OR = 1.4, 95 % CI = 1.06-1.85, p = 0.016).

Conclusions: The present study indicates lack of a direct influence of MMP-7 A-181G polymorphism on the risk of preeclampsia. However, this polymorphism through elevation of MDA level as a marker of lipid peroxidation and interaction with MMP-9 C-1562T polymorphism might be associated with the risk of severe preeclampsia.
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http://dx.doi.org/10.1007/s00404-014-3376-4DOI Listing
January 2015

Endothelial Nitric Oxide Synthase (eNOS) 4a/b and G894T Polymorphisms and Susceptibility to Preeclampsia.

J Reprod Infertil 2013 Oct;14(4):184-9

Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Preeclampsia is a pregnancy complication with unknown etiology and its incidence is associated with genetic and environmental factors. There are inconsistent reports related to the role of endothelial nitric oxide synthase (eNOS) 4a/b polymorphism on the risk of preeclampsia development. The aim of the present study was to investigate the possible influence of eNOS 4a/b and its synergism with eNOS G894T polymorphism on the risk of preeclampsia.

Methods: The present case-control study consisted of 179 unrelated women with preeclampsia including 118 with mild and 61 with severe preeclampsia and 96 unrelated women with normal pregnancy as controls. All studied women were from Kermanshah Province of Iran. eNOS 4a/b and G894T genotypes were detected using polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. The categorical variables between groups were compared using χ(2) test and the Odds ratios (OR) were obtained by SPSS logistic regression. Statistical significance was assumed at p<0.05 level.

Results: The frequency of eNOS a allele was slightly higher in both mild (16.5%) and severe (17.2%) preeclamptic women than controls (15.1%). Also, no significant difference was found between early- and late-onset preeclamptic women regarding the distribution of eNOS 4a/b genotypes. The presence of each allele of eNOS a or T was not associated with the risk of preeclampsia. However, the concomitant presence of both eNOS a and T alleles was associated with a non significant increased risk of severe preeclampsia by 1.77-fold (p=0.35).

Conclusion: The present study indicates the lack of association between eNOS a and T alleles with the risk of mild preeclampsia and a non significant increased risk of severe preeclampsia in the presence of both alleles which needs to be investigated in a study with larger samples.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911813PMC
October 2013

AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia.

Gene 2014 Mar 15;538(1):176-81. Epub 2014 Jan 15.

Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A polymorphism with susceptibility to preeclampsia was studied in 252 women consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166 A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and 48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%, respectively). The presence of G allele was associated with 1.69-fold increased risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and diastolic blood pressures in the presence of GG+GA genotype were significantly higher compared to those in the presence of AA genotype. The concomitant presence of both alleles of AT2R G and AT1R C was associated with 1.3 times increased risk of mild preeclampsia (p=0.03). There was an interaction between AT2R G and ACE D alleles that significantly increased the risk of mild and severe preeclampsia by 1.38- and 1.3-fold, respectively. Also, interaction between MMP-9 T and AT2R G alleles increased the risk of severe preeclampsia 1.39-fold (p=0.028). Our study demonstrated that the G allele of AT2R -1332 G:A polymorphism is associated with an increased risk of preeclampsia. Also, epistatic interaction of G allele and each allele of the AT1R C, ACE D and MMP-9 T was associated with the risk of preeclampsia. Our findings suggest that the renin-angiotensin system (RAS) variants and gene-gene interactions affect the risk of preeclampsia.
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http://dx.doi.org/10.1016/j.gene.2013.12.013DOI Listing
March 2014

Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress.

J Matern Fetal Neonatal Med 2013 Nov 23;26(16):1590-4. Epub 2013 May 23.

Medical Biology Research Center .

Objective: To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women.

Methods: In a case-control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively.

Results: The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE ε3ε4 compared to ε3ε3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level.

Conclusions: Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.
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http://dx.doi.org/10.3109/14767058.2013.795534DOI Listing
November 2013

eNOS 4a/b polymorphism and its interaction with eNOS G894T variants in type 2 diabetes mellitus: modifying the risk of diabetic nephropathy.

Dis Markers 2013 ;34(6):437-43

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

To investigate the possible association between eNOS 4a/b polymorphism and the risk of developing type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) 173 T2DM patients with and without DN and 101 healthy subjects with ethnic background of Kurds were examined for the frequency of eNOS variants using PCR-RFLP method. The frequency of eNOS 4a/b genotypes between T2DM and controls was not significantly difference. Studying eNOS 4a/b variants alone indicated that the presence of eNOS 4a allele was not associated with the risk of developing DN. However, considering both polymorphisms of eNOS 4a/b and G894T indicated that the risk of macroalbuminuria significantly increased in the presence of either eNOS 4a or 894T allele by 2.45 times (p=0.014) and 3.7-fold (p=0.016), respectively. However, the concomitant presence of both alleles was not associated with the risk of macroalbuminuria. In microalbuminuric patients, in the presence of each allele, the risk of microalbuminuria increased 2.2 times (p=0.028) and 2.72-fold (p=0.057) for eNOS 4a and 894T alleles, respectively. However, the combined presence of both eNOS 894T and 4a alleles was not associated with the risk of microalbuminuria. The present study indicates the absence of association between eNOS 4a/b variants and the risk of developing T2DM and DN. Also, we demonstrated that eNOS 4a or 894T allele alone increased the risk of developing DN but this effect was modified by the concomitant presence of both alleles.
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http://dx.doi.org/10.3233/DMA-130988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810362PMC
October 2013

MMP-9 (-1562 C:T) polymorphism as a biomarker of susceptibility to severe pre-eclampsia.

Biomark Med 2013 Feb;7(1):93-8

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Aim: To investigate the role of MMP-9 (-1562 C:T) polymorphism as a biomarker for susceptibility to pre-eclampsia.

Patients & Methods: MMP-9 variants were detected in 160 women with mild and severe pre-eclampsia and 112 healthy pregnant women.

Results: A significantly higher frequency of MMP-9 CT genotype was observed in both mild and severe pre-eclamptic women compared with controls. In the presence of CT + TT genotype the risk of severe pre-eclampsia increased 2.37-fold (p = 0.02). In women with early-onset pre-eclampsia the frequency of MMP-9 CT + TT genotype was significantly higher (p = 0.045) compared with those with late-onset pre-eclampsia.

Conclusion: The MMP-9 variant could be a useful biomarker of susceptibility to severe pre-eclampsia and early-onset severe pre-eclampsia.
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http://dx.doi.org/10.2217/bmm.12.95DOI Listing
February 2013

AT2R -1332 G:A polymorphism and diabetic nephropathy in type 2 diabetes mellitus patients.

J Renal Inj Prev 2013 1;2(3):97-101. Epub 2013 Sep 1.

Department of Biochemistry, Sanandaj Science and Research Branch, Islamic Azad University, Sanandaj, Iran.

Introduction: The rennin-angiotensin system (RAS) plays a central role in the regulation of sodium metabolism, vascular tone, blood pressure, renal hemodynamics, and vascular modeling and is activated by hyperglycemiaObjectives: In the present study the influence of AT2R -1332 G:A polymorphism on the risk of T2DM and its complications in a population from Western Iran has been investigated.

Patients And Methods: In a case-control study, 70 individuals with type 2 diabetes mellitus (T2DM) including normo-, micro- and macro-albuminuric patients and 112 healthy subjects from the Kermanshah province were studied to investigate the association between the angiotensin type 2 receptor (AT2R) -1332 G:A variants with the risk of T2DM and its complications. The genotypes of the AT2R were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Analysis of AT2R -1332 G:A polymorphism indicated the absence of association between this polymorphism with T2DM and diabetic nephropathy.

Results: Analysis of AT2R -1332 G:A polymorphism indicated the absence of association between this polymorphism with T2DM and diabetic nephropathy. In females with diabetic nephropathy a significantly higher frequency of AA genotype (50%) was detected compared to those without nephropathy (13.3%, p=0.015). The presence of A allele of AT2R was associated with significantly (p=0.029) increased risk of coronary artery disease (CAD) in diabetic patients without nephropathy.

Conclusion: Our study indicated an association between the AT2R -1332 G:A polymorphism and the risk of diabetic nephropathy in females only. Also, the A allele was associated with the risk of CAD in those diabetic patients without nephropathy.
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http://dx.doi.org/10.12861/jrip.2013.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206021PMC
October 2014

Synergistic effects of angiotensinogen -217 G→A and T704C (M235T) variants on the risk of severe preeclampsia.

J Renin Angiotensin Aldosterone Syst 2014 Jun 23;15(2):156-61. Epub 2012 Nov 23.

Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Iran Medical Biology Research Center, Kermanshah University of Medical Sciences, Iran

Background: The rate-limiting step of the renin-angiotensin system is the enzymatic cleavage of angiotensinogen (AGT) by renin. The aims of the present study were to investigate the association between AGT T704C (M235T) and -217 G→A polymorphisms with the risk of preeclampsia and synergistic effects of both polymorphisms on the susceptibility to preeclampsia.

Methods: We studied AGT variants in 170 women with preeclampsia, including 84 women with mild and 86 women with severe forms of preeclampsia, and 100 age and parity matched controls.

Results: There was a trend towards increased risk of severe preeclampsia in the presence of -217 AA (odds ratio (OR)=1.5, 95% confidence interval (CI)= 0.38-5.84, p=0.57) and TC+CC genotypes (OR=1.32, 95% CI= 0.67-2.58, p=0.42). However, the interaction of both alleles of -217A and 704C highly increased the risk of severe preeclampsia, by 2.23-fold, although this did not reach statistical significance. The frequency of the CC genotype of the T704C polymorphism in early-onset preeclampsia tended to be higher (35%) compared with that in patients with late-onset preeclampsia (21.7%).

Conclusions: The present study demonstrates that both variants of AGT -217 G→A and T704C might work in synergism to influence the risk of severe preeclampsia, which needs to be confirmed in studies with larger sample size.
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http://dx.doi.org/10.1177/1470320312467555DOI Listing
June 2014

Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus.

Hum Genomics 2012 Sep 25;6:20. Epub 2012 Sep 25.

Medical Biology Research Center, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: The present study was conducted to investigate the possible outcome of interaction between endothelial nitric oxide (NOS3) G894T and cholesteryl ester transfer TaqIB variants on the risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). The sample included a total of 207 CAD patients (102 CAD patients with T2DM and 105 CAD patients without T2DM). There were also 101 patients with T2DM and 92 age- and sex-matched healthy individuals as controls. All study participants were from Western Iran. The sample was genotyped by polymerase chain reaction-restriction fragment length polymorphism.

Results: The presence of NOS3 T allele was not associated with the risk of CAD or T2DM, and the CETP B1 allele was only significantly associated with the increased risk of CAD in total CAD patients (odds ratio (OR) = 5.1, p = 0.019). However, the concomitant presence of both CETP B1 and NOS3 T alleles significantly increased the risk of CAD in total CAD patients (OR = 18.1, p < 0.001), in CAD patients without T2DM (OR = 27.1, p = 0.03), and in CAD patients with T2DM (OR = 13.5, p = 0.002). Also, the presence of both alleles increased the risk of T2DM (OR = 12, p = 0.004).

Conclusions: Our findings, for the first time, indicate that NOS3 T allele strongly interacts with CETP B1 allele to augment the risk of CAD and T2DM in the population of Western Iran.
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http://dx.doi.org/10.1186/1479-7364-6-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500247PMC
September 2012