Publications by authors named "HyungChul Rah"

28 Publications

  • Page 1 of 1

Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells.

PLoS One 2017 25;12(8):e0183479. Epub 2017 Aug 25.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulosa cell. In each case, mRNAs were up or down-regulated after treatments with miR-146a C or G and miR-196a2 T or C. We found that miR-146a led to a significantly altered regulation of the mRNA levels of FOXO3, FOXL2 and CCND2 compared to controls. We also found that the polymorphisms of miR-146a led to a significantly altered regulation of CCND2 and FOXO3. Our results suggest that miR-146aC>G and miR-196a2T>C can regulate the levels of many of their target transcripts. In addition, specific target genes of miR-146aC>G polymorphisms may be involved in granulosa cell regulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183479PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571913PMC
October 2017

miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent pregnancy loss.

PLoS One 2017 10;12(5):e0177160. Epub 2017 May 10.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

Objective: MicroRNAs (miRNAs) regulate gene expression during the peri-implantation period. The purpose of this study was to investigate whether genetic polymorphisms in the four miRNAs associated with fetal or placental development play roles in the development of idiopathic recurrent pregnancy loss (RPL) in Korean females.

Study Design: A case-control study involving 225 controls and 387 women with at least two consecutively recurrent pregnancy losses between 1999 and 2012 was performed. The genotypes of the four miRNA polymorphisms, including miR-27a rs895819, miR-423 rs6505162, miR-449b rs10061133, and miR-605 rs2043556, were analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals were estimated using multivariate analyses after maternal age adjustments. The relationships between each of the four microRNA genotypes and each of the six clinical parameters of the RPL patients (plasma homocysteine and folate levels, natural killer cell number, platelet count, prothrombin time, and, activated partial thromboplastin time) were analyzed using multiple linear regression analyses.

Results: Our results suggest that weak associations between decreased RPL risk and the genotypes of miR-27a (AG and AG+GG), combination genotype of miR-27a/miR-423 (AG/GC), and haplotypes of miR-27a/miR-423/miR-449b/miR-605 (G-C-A-G) and miR-27a/miR-449b/miR-605 (G-A-G), whereas weak associations between increased RPL risk and genotypes of miR-449b (GG and AG+GG), combination genotypes of miR-423/miR-449b (CC/GG and CA/AG), miR-449b/miR-605 (AG/AG), haplotypes of miR-27a/miR-423/miR-449b/miR-605 (A-C-G-A, A-A-A-G, and G-C-G-G), miR-27a/miR-423/miR-449b (A-C-G), miR-27a/miR-449b/miR-605 (A-A-G, A-G-A, and G-G-G), miR-423/miR-449b/miR-605 (C-G-G and A-A-G), and miR-423/miR-449b (C-G and A-A). The genotypes of miR-27a (AG and AG+GG) also showed significant contributions to the prediction of folate levels in RPL patients.

Conclusions: The study showed associations between miRNA polymorphisms (miR-27a rs895819 and miR-449b rs10061133) and RPL development, and between the miRNA polymorphism (miR-27a rs895819) and plasma folate levels.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177160PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425187PMC
September 2017

Polymorphisms in tumor necrosis factor-alpha (-863C>A, -857C>T and +488G>A) are associated with idiopathic recurrent pregnancy loss in Korean women.

Hum Immunol 2016 Jun 12;77(6):506-11. Epub 2016 Apr 12.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam 13496, South Korea; Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, South Korea. Electronic address:

Polymorphisms in TNF-a have been reported as genetic risk factors for recurrent spontaneous abortion and TNF-α may be immunologically important. We therefore examined the contribution of several TNF-a mutations to this phenomenon. The study participants consisted of 388 patients with idiopathic recurrent pregnancy loss (RPL), which was diagnosed on the basis of at least two consecutive spontaneous abortions; control subjects were 224 healthy women with a history of successful pregnancies. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to determine the TNF-α -863C>A, -857C>T, and +488G>A genotypes. The TNF-α -863C>A variants correlated with increased risk of RPL (CA+AA; adjusted odds ratio [AOR], 2.142; 95% confidence interval [CI], 1.493-3.074). These data did not differ in a stratified analysis according to number of consecutive spontaneous abortions. In haplotype analysis, there were similar trends of data for combination analysis, but in patients with 3+ pregnancy losses, a stratified analysis revealed that this correlation did not increase directly with the number of pregnancy losses. The TNF-α -863C>A variant is a possible genetic risk factor for idiopathic RPL in Korean women.
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http://dx.doi.org/10.1016/j.humimm.2016.04.012DOI Listing
June 2016

Whole genome sequencing in cats, identifies new models for blindness in AIPL1 and somite segmentation in HES7.

BMC Genomics 2016 Mar 31;17:265. Epub 2016 Mar 31.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, E109 Vet Med Building, 1600 E. Rollins Street, Columbia, MO, 65211, USA.

Background: The reduced cost and improved efficiency of whole genome sequencing (WGS) is drastically improving the development of cats as biomedical models. Persian cats are models for Leber's congenital amaurosis (LCA), the most severe and earliest onset form of visual impairment in humans. Cats with innocuous breed-defining traits, such as a bobbed tail, can also be models for somite segmentation and vertebral column development.

Methods: The first WGS in cats was conducted on a trio segregating for LCA and the bobbed tail abnormality. Variants were identified using FreeBayes and effects predicted using SnpEff. Variants within a known haplotype block for cat LCA and specific candidate genes for both phenotypes were prioritized by the predicted variant effect on the proteins and concordant segregation within the trio. The efficiency of WGS of a single trio of domestic cats was evaluated.

Results: A stop gain was identified at position c.577C > T in cat AIPL1, a predicted p.Arg193*. A c.5A > G variant causing a p.V2A was identified in HES7. The variants segregated concordantly in a Persian - Japanese bobtail pedigree. Over 1700 cats from 40 different breeds and populations were genotyped for the AIPL1 variant, defining an allelic frequency in only Persian -related breeds of 1.15%. A sub-set of cats was genotyped for the HES7 variant, supporting the variant as private to the Japanese bobtail breed. Approximately 18 million SNPs were identified for application in cat research. The cat AIPL1 variant would have been considered a high priority variant for evaluation, regardless of a priori knowledge from previous genetic studies.

Conclusions: This study represents the first effort of the 99 Lives Cat Genome Sequencing Initiative to identify disease--causing variants in the domestic cat using WGS. The current cat reference assembly is efficient for gene and variant identification. However, as the feline variant database improves, development of cats as biomedical models for human disease will be more efficient, providing an alternative, large animal model for drug and gene therapy trials. Undiagnosed human patients with early-onset blindness should be screened for this AIPL1 variant. The HES7 variant should further calibrate the somite segmentation clock.
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http://dx.doi.org/10.1186/s12864-016-2595-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815086PMC
March 2016

Genetic variants of vascular endothelial growth factor are associated with recurrent implantation failure in Korean women.

Reprod Biomed Online 2016 Feb 23;32(2):190-6. Epub 2015 Nov 23.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea. Electronic address:

Vascular endothelial growth factor (VEGF) is involved in embryonic development, decidual vascularization and placenta angiogenesis. This study was performed to determine whether there is an association between genetic polymorphisms in the VEGF gene and the development of recurrent implantation failure (RIF) in Korean women. A total of 119 women diagnosed with RIF and 236 control subjects were genotyped for VEGF polymorphic sites including rs833061 (-460T>C), rs25648 (-7C>T) and rs3025020 (-583C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays and real-time PCR. The VEGF rs833061 C allele and rs25648 T allele were significantly associated with increased RIF risk (odds ratio [OR] = 1.813 [1.161-2.831], P = 0.009, OR = 2.213 [1.254-3.903], P = 0.005). The rs833061/rs25648 TC/CT, TC/CT+TT, and rs833061/rs3025020 TC+CC/TT genotypes were more frequent in the RIF group compared with the control group (OR = 2.130 [1.092-4.156], P = 0.025, OR = 2.130 [1.092-4.156], OR = 4.261 [1.163-15.620], P = 0.028, respectively). The results of this study suggests that VEGF polymorphisms are associated with RIF development. Therefore, we postulate that VEGF polymorphisms might be useful markers to predict RIF development. Further studies are warranted to elucidate the role of VEGF variants and RIF development.
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http://dx.doi.org/10.1016/j.rbmo.2015.10.010DOI Listing
February 2016

Association of breast cancer-related microRNA polymorphisms with idiopathic primary ovarian insufficiency.

Menopause 2015 Apr;22(4):437-43

From the 1Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; 2Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea; 3Department of Obstetrics and Gynecology and Fertility Center of CHA Bundang Medical Center, CHA University, Seongnam, South Korea; and 4Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, South Korea.

Objective: The aim of our study was to investigate whether breast cancer-related microRNA polymorphisms are associated with primary ovarian insufficiency (POI) risk.

Methods: Four breast cancer-related microRNA polymorphisms (miR-27aA > G [rs895819], miR-135bC > T [rs74141216], miR-423C > A [rs6505162], and miR-608G > C [rs4919510]) were genotyped in 136 women with idiopathic POI and 224 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between cases and controls were compared. Odds ratios and 95% CIs were determined as measures of the strength of association between genotype and POI.

Results: Two haplotypes (G-C-A-G and A-T-C-C) of miR-27a/miR-135b/miR-423/miR-608 were associated with increased POI risk. The haplotypes G-A-G of miR-27a/miR-423/miR-608 and A-T-C of miR-27a/miR-135b/miR-608 were associated with higher POI risk, whereas the G-T haplotype of miR-27a/miR-135b was associated with decreased POI risk. The association between POI risk and the G-A-G haplotype of miR-27a/miR-423/miR-608 remained significant after false discovery rate correction for multiple comparisons. The combined genotypes AA/CT/CC/CC, AG/CC/CA/GC, GG/CC/CC/CC, and GG/CC/CA/GG of miR-27a/miR-135b/miR-423/miR-608 were also associated with higher POI risk. Increased POI risk was observed in combined genotypes GG/CC/GG of miR-27a/miR-135b/miR-608; AA/CC/GC, AG/CA/GC, GG/CC/GG, GG/CC/CC, and GG/CA/GG of miR-27a/miR-423/miR-608; and GG/GG of miR-27a/miR-608; however, these associations were not significant after false discovery rate correction. None of the four microRNA polymorphisms alone was associated with POI risk.

Conclusions: Our data suggest that breast cancer-related microRNA polymorphisms, including miR-27aA > G, miR-423C > A, and miR-608G > C, are associated with increased POI risk via interactions between miR-27aG, miR-423A, and miR-608G variants. However, our results should be interpreted cautiously because of our small sample size and the low statistical power of our study design.
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http://dx.doi.org/10.1097/GME.0000000000000325DOI Listing
April 2015

Genetic variants in microRNA machinery genes are associated [corrected] with idiopathic recurrent pregnancy loss risk.

PLoS One 2014 25;9(4):e95803. Epub 2014 Apr 25.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea.

Objective: Key molecules involved in microRNA (miRNA) biogenesis, such as DROSHA, XPO5, and DICER, have been identified in trophoblast cells, confirming that the miRNA biogenesis pathway is active in human placenta. In addition, miRNAs regulate uterine gene expression associated with inflammatory responses during the peri-implantation period and participate in maternal-fetal immune tolerance. The purpose of this study was to demonstrate whether genetic polymorphisms in miRNA machinery genes show an association with idiopathic recurrent pregnancy loss (RPL) in Korean women.

Study Design: We performed a case-control study with 238 controls and 338 women who had experienced at least two consecutive pregnancy losses between 1999 and 2010. Genotypes of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN GTPase (RAN) rs14035, and exportin-5 (XPO5) rs11077 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The logistic odds ratios (ORs) of RPL were estimated with a 95% confidence interval (CI) in multivariate analysis after maternal age adjustment. Gene-gene interactions among the loci of the four gene polymorphisms were evaluated using the multifactor dimensionality reduction (MDR) method.

Results: The RAN rs14035 CC genotype and DICER rs3742330/DROSHA rs10719 GG/TC+CC, rs3742330/RAN rs14035 GG/CC, and DICER rs3742330/XPO5 rs11077 GG/AC+CC combinations were significantly associated with increased RPL risk, whereas the RAN rs14035 CT, DICER rs3742330/RAN rs14035 AA+AG/CT+TT, DROSHA rs10719/RAN rs14035 TC+CC/CT+TT, and RAN rs14035/XPO5 rs11077 CT+TT/AA combinations reduced RPL risk. The A-T-T-C and G-C-T-A allele combinations (DICER/DROSHA/RAN/XPO5) were 20 times more frequent in the RPL group than in the control group.

Conclusion: Our study demonstrates the relationship between RPL development and the polymorphism of the miRNA machinery gene RAN and combined genotype of DROSHA/DICER.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095803PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000197PMC
January 2015

Transcobalamin II (TCN2 67A>G and TCN2 776C>G) and transcobalamin II receptor (TCblR 1104C>T) polymorphisms in Korean patients with idiopathic recurrent spontaneous abortion.

Am J Reprod Immunol 2014 Sep 18;72(3):337-46. Epub 2014 Apr 18.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Problem: The transcobalamin II (TCN2) 776C>G polymorphism has been reported to be a genetic risk factor for idiopathic recurrent spontaneous abortion (RSA). However, the sample size in previous studies was small, and other TCN2 polymorphisms have not been studied. Moreover, the TCN2 67A>G and 776C>G polymorphisms, and the transcobalamin II receptor (TCblR/CD320) 1104C>T polymorphism, have demonstrated associations with immune responses.

Method Of Study: Three hundred and seventy-eight RSA patients who had at least two consecutive spontaneous abortions were enrolled. Two hundred and seven control subjects were collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the TCN2 67A>G and 776C>G polymorphisms, and the TCblR 1104C>T polymorphism.

Results: RSA patients showed significantly different frequencies of the TCN2 67AG+GG genotypes compared with control subjects.

Conclusion: The TCN2 67G allele is a possible risk factor for idiopathic RSA.
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http://dx.doi.org/10.1111/aji.12256DOI Listing
September 2014

Divergent and dynamic activity of endogenous retroviruses in burn patients and their inflammatory potential.

Exp Mol Pathol 2014 Apr 6;96(2):178-87. Epub 2014 Feb 6.

Shriners Hospitals for Children Northern California, Sacramento, CA 95817, USA; Department of Surgery, University of California, Davis, Sacramento, CA 95817, USA. Electronic address:

Genes constitute ~3% of the human genome, whereas human endogenous retroviruses (HERVs) represent ~8%. We examined post-burn HERV expression in patients' blood cells, and the inflammatory potentials of the burn-associated HERVs were evaluated. Buffy coat cells, collected at various time points from 11 patients, were screened for the expression of eight HERV families, and we identified their divergent expression profiles depending on patient, HERV, and time point. The population of expressed HERV sequences was patient-specific, suggesting HERVs' inherent genomic polymorphisms and/or differential expression potentials depending on characteristics of patients and courses of injury response. Some HERVs were shared among the patients, while the others were divergent. Interestingly, one burn-associated HERV gag gene from a patient's genome induced IL-6, IL-1β, Ptgs-2, and iNOS. These findings demonstrate that injury stressors initiate divergent HERV responses depending on patient, HERV, and disease course and implicate HERVs as genetic elements contributing to polymorphic injury pathophysiology.
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http://dx.doi.org/10.1016/j.yexmp.2014.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104748PMC
April 2014

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women.

Maturitas 2014 Feb 31;77(2):163-7. Epub 2013 Oct 31.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea. Electronic address:

Objective: The aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.

Study Design: We genotyped the INHA polymorphisms c.-16C>T (rs35118453) and c.-124A>G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.

Results: There were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T-G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR=1.630, 95% CI=1.081-2.457). Combination genotype analysis showed that the CT+TT/GG genotype frequency was higher in POI patients than in the controls (OR=2.414, 95% CI=1.190-4.895).

Conclusions: We provide evidence to suggest that when the two variant alleles are combined, the c.-16C>T and c.-124A>G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.
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http://dx.doi.org/10.1016/j.maturitas.2013.10.015DOI Listing
February 2014

Genetic association of five plasminogen activator inhibitor-1 (PAI-1) polymorphisms and idiopathic recurrent pregnancy loss in Korean women.

Thromb Haemost 2013 Oct 1;110(4):742-50. Epub 2013 Aug 1.

Nam Keun Kim, PhD, Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 351 Yatap-dong, Bundang-gu, Seongnam 463-712, South Korea, Tel.: +82 31 780 5762, Fax: +82 31 780 5766, E-mail:

Plasminogen activator inhibitor-1 (PAI-1) is important for maintaining pregnancy. Aberrantly increased PAI-1 levels may contribute to thrombosis and inflammation, leading to pregnancy loss. This study investigated the association of PAI-1 polymorphisms (PAI-1 rs2227631 [-844G>A], rs1799889 [-675 4G/5G], rs6092 [43G>A], rs2227694 [9785G>A], and rs7242 [11053T>G]) with idiopathic recurrent pregnancy loss (RPL) in Korean women. We screened 308 RPL patients and 227 control participants for five PAI-1 polymorphisms. Genotyping of PAI-1 was performed by polymerase chain reaction-restriction fragment length polymorphism assay. PAI-1 4G4G and -844AA/4G4G/11053GG genotypes were associated with RPL. PAI-1 -844A/4G/43G/9785G/11053G haplotype was connected to hypofibrinolytic status (i.e. increased levels of plasma PAI-1, increased numbers of platelets, reduced prothrombin time, and reduced activated partial thromboplastin time). Moreover, PAI-1 11053TG+GG frequency was positively related to plasma homocysteine and urate levels, whereas -844AA frequency was associated with plasma folate concentrations according to ordinal logistic regression analysis. Based on these results, we propose that PAI-1 -844G>A, 4G/5G, and 11053T>G polymorphisms are markers of RPL.
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http://dx.doi.org/10.1160/TH13-03-0242DOI Listing
October 2013

Association between polymorphisms in renin-angiotensin system genes and primary ovarian insufficiency in Korean women.

Menopause 2013 May;20(5):561-7

Department of Obstetrics and Gynecology, School of Medicine, College of Life Science, CHA University, Seongnam, South Korea.

Objective: The purpose of this study was to evaluate the relationship between angiotensin-converting enzyme (ACE; insertion/deletion), angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) and the prevalence of primary ovarian insufficiency (POI) in Korean women.

Methods: A total of 133 women with POI and 238 controls were genotyped for polymorphic sites in each gene using polymerase chain reaction-restriction fragment length polymorphism analysis.

Results: ACE ID and ID + II variants occurred more frequently in women with POI than in controls (odds ratio [OR], 1.830; 95% CI, 1.040-3.221; P = 0.040; and OR, 1.797; 95% CI, 1.055-3.060; P = 0.031, respectively). The AT1R 1166AC genotype occurred more frequently in participants with POI than in controls (OR, 3.171; 95% CI, 1.562-6.436; P = 0.002). Comparing the combined genotype frequencies of ACE/AT1R revealed that the frequencies of ID/AA, ID/AC, and II/AC were higher in participants than in controls (OR, 1.916; 95% CI, 1.053-3.485; P = 0.043; OR, 3.544; 95% CI, 1.207-10.407; P = 0.036; and OR, 7.875; 95% CI, 2.224-27.881; P = 0.001, respectively). The TT/AC genotype for combined genotyping of AGT/AT1R was more frequently observed in the POI group than in the control group (OR, 3.472; 95% CI, 1.450-8.313; P = 0.006). In multifactor dimensionality reduction-based haplotype analysis, the I-T-C genotype of ACE/AGT/AT1R was a possible predisposing factor for POI (OR, 4.678; 95% CI, 1.721-12.717; P = 0.002).

Conclusions: This study demonstrates that polymorphisms in the renin-angiotensin system are related to the prevalence of POI. Thus, these renin-angiotensin system genes may serve as a novel marker for predicting the development of POI.
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http://dx.doi.org/10.1097/GME.0b013e3182733921DOI Listing
May 2013

Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women.

Menopause 2013 Oct;20(10):1067-73

From the 1Department of Biomedical Science, College of Life Science, 2Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea; 3Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, South Korea; and 4Department of Obstetrics and Gynecology and Fertility Center, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Objective: The aim of our study was to investigate whether polymorphisms in microRNA machinery genes are associated with the risk of primary ovarian insufficiency (POI).

Methods: We genotyped 136 POI patients and 236 controls among Korean women for nine single nucleotide polymorphisms (SNPs; DROSHA rs6877842 and rs10719; DICER1 rs13078 and rs3742330; RAN rs14035; and XPO5 rs34324334, rs2257082, rs11544382, and rs11077) by polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as measures of the strength of the association between genotype and POI.

Results: Of the nine SNPs, XPO5 rs34324334 and rs11544382 were monomorphic and were not analyzed further. The XPO5 rs2257082 CT and CT + TT variant genotypes were more frequent in patients (OR, 2.097; 95% CI, 1.207-3.645) than in controls (OR, 2.030; 95% CI, 1.196-3.445). The combined frequencies of XPO5 rs2257082 CT + TT and rs11077 AC + CC genotypes were higher in patients than in controls (OR, 2.526; 95% CI, 1.088-5.865). An association of POI risk with other polymorphisms was not found. A haplotype-based analysis of seven polymorphisms of the microRNA machinery genes for gene-gene interactions suggests that ***ACTA, ***GCCA, ***G*C*, *T*ATTA, and ***ACT* haplotypes (asterisk indicates SNP locus not included; DROSHA rs6877842 and rs10719, DICER1 rs13078 and rs3742330, RAN rs14035, and XPO5 rs2257082 and rs11077 polymorphisms) are associated with higher POI prevalence, and that ***GCTA, ***ACCA, *C*ATTA, and *C*ATT* haplotypes are associated with lower POI prevalence.

Conclusions: Our data demonstrate that the XPO5 rs2257082 T variant allele occurs more frequently in POI patients than in controls, suggesting that this allele may be associated with increased POI risk.
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http://dx.doi.org/10.1097/GME.0b013e3182883907DOI Listing
October 2013

Association between polymorphisms in the renin-angiotensin system genes and prevalence of spontaneously aborted fetuses.

Am J Reprod Immunol 2013 Sep 11;70(3):238-45. Epub 2013 Mar 11.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Problem: The renin-angiotensin system is associated with angiogenesis, tissue remodeling, prenatal development, and Th2 cytokine production. The purpose of this study was to evaluate whether polymorphisms in angiotensin I-converting enzyme [ACE insertion/deletion (I/D)], angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) affect the prevalence of spontaneously aborted fetuses (SAFs).

Method Of Study: One hundred and ninety-eight SAFs were <20 weeks of gestational age. The control subjects were 103 healthy children and 640 adults collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the ACE I/D, AGT M235T, and AT1R 1166A>C genotypes.

Results: II/MM/AA, II/MT/AA, and II/TT/AC of ACE/AGT/AT1R were significantly different from controls. In particular, the statistical significance of the II/MM/AA genotype remained strong in chromosomally normal SAFs.

Conclusion: Our data suggest that the II/MM/AA of ACE/AGT/AT1R is a possible predisposing factor for spontaneous abortion.
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http://dx.doi.org/10.1111/aji.12110DOI Listing
September 2013

Association of nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) with primary ovarian insufficiency in Korean women.

Maturitas 2013 Feb 22;74(2):160-5. Epub 2012 Nov 22.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

Objectives: The aim of our study was to investigate whether the endothelial nitric oxide synthase (eNOS) gene polymorphisms -786T>C, 4a4b, and 894G>T that affect nitric oxide (NO) generation confer a risk for primary ovarian insufficiency (POI) in Korean women.

Study Design: We genotyped 136 POI patients and 236 controls among Korean women for the three single nucleotide polymorphism sites with PCR-RFLP analysis. Differences in the eNOS -786T>C (rs2070744), 4a4b (rs61722009), and 894G>T (rs1799983) genotype frequencies between patients and controls were compared, and odds ratios and 95% confidence intervals were determined as a measure of the strength of the association between the genotypes and POI.

Results: The POI patients had significantly decreased frequencies of the eNOS 894GT and -786TT/894GT genotypes (P=0.025 and 0.027, respectively). However, the significant association between these eNOS polymorphisms and POI disappeared after adjustment for multiple comparisons (adjusted P=0.075 and 0.081, respectively). The eNOS -786T/894G haplotype is more frequent in patients than controls (P=0.030), whereas the -786T/894T haplotype was less frequent in patients (P=0.031). The associations between -786/894 haplotypes and POI were confirmed by permutation tests. We did not find associations between the eNOS -786T>C or 4a4b polymorphisms and POI.

Conclusions: Our data suggest that the eNOS -786T/894T haplotype is associated with a decreased POI risk, and we postulate that the eNOS -786T/894T haplotype may confer less risk on POI occurrence by reducing pathologically increased NO generation by eNOS in POI. Further study is warranted to elucidate the effect of the eNOS 894G>T polymorphism and POI occurrence.
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http://dx.doi.org/10.1016/j.maturitas.2012.10.018DOI Listing
February 2013

Association of kinase insert domain-containing receptor (KDR) gene polymorphisms with idiopathic recurrent spontaneous abortion in Korean women.

Fertil Steril 2013 Mar 14;99(3):753-760.e8. Epub 2012 Nov 14.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

Objective: To investigate whether kinase insert domain-containing receptor (KDR) gene polymorphisms are risk factors for recurrent spontaneous abortion (RSA) in Korean women.

Design: Case-control study.

Setting: University hospital.

Patient(s): Three hundred twenty-seven idiopathic RSA patients and 230 controls with Korean ethnicity.

Intervention(s): None.

Main Outcome Measure(s): The KDR -604T→C (rs2071559), 1192G→A (rs2305948), and 1719A→T (rs1870377) polymorphisms were assessed.

Result(s): KDR -604TC and TC+CC genotypes were more prevalent in RSA patients than in controls (adjusted odds ratio [AOR] = 2.091 and 2.076, respectively). KDR -604TC+CC/1192GG, -604TC+CC/1719AA, and -604TC+CC/1719TA+TT combined genotypes exhibited higher frequencies in RSA patients (AOR = 2.422, 2.611, and 2.216, respectively). KDR -604C/1192G/1719A, -604C/1192G/1719T, -604C/1192G, -604C/1719A, and -604C/1719T haplotype frequencies were higher in RSA patients (OR = 1.778, 2.659, 2.089, 1.678, and 1.806, respectively), whereas -604T/1192G/1719A, -604T/1192G, and -604T/1719A haplotype frequencies were lower in RSA patients (OR = 2.422, 2.611, and 2.216, respectively). No association was found between RSA and KDR 1192G→A or 1719A→T.

Conclusion(s): An association between the KDR -604T→C polymorphism and RSA was found in Korean women. Carriers of the -604C variant allele were more frequent among RSA patients than among controls, suggesting that KDR -604C may confer RSA risk. The association of 1719A→T with RSA that was found in Taiwanese Han women was not observed in Korean women.
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http://dx.doi.org/10.1016/j.fertnstert.2012.10.038DOI Listing
March 2013

Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G polymorphisms with gastric cancer risk and survival in the Korean population.

Mol Carcinog 2013 Nov 21;52 Suppl 1:E39-51. Epub 2012 Sep 21.

Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

We investigated whether four common microRNA polymorphisms (miR-146aC>G [rs2910164], miR-149T>C [rs2292832], miR-196a2T>C [rs11614913], and miR-499A>G [rs3746444]) are associated with the susceptibility and prognosis of gastric cancer in the Korean population. The four microRNA single-nucleotide polymorphisms (SNPs) were identified in a case-control study (461 patients; 447 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in the Korean population. When patients were stratified into diffuse and intestinal-type gastric cancer groups, subjects with the miR-499AG and AG + GG genotypes had reduced adjusted odds ratios (AORs) for diffuse-type gastric cancer (AOR = 0.54 with 95% confidence interval [CI] = 0.31-0.97; AOR = 0.57 with 95% CI = 0.33-0.97). In the stratified analyses for gastric cancer risk, the miR-146aGG and CG + GG genotypes were associated with increased risk of gastric cancers among the non-smokers, whereas the miR-149TC and TC + CC genotypes showed lower risk of gastric cancer in males. The miR-196a2CC genotype was associated with elevated gastric cancer risk among females. For gastric cancer prognosis, intestinal-type gastric cancer patients with miR-146aCG + GG genotypes had significantly higher survival rates (log-rank P = 0.030) than patients with the CC genotype, and patients with the miR-499AA genotype had significantly increased survival rates compared to patients with the AG + GG genotypes (log-rank P = 0.013). When miR-146aCG + GG and miR-499AA genotypes were combined, the survival rate of intestinal-type gastric cancer patients was elevated (log-rank P < 0.001). No association was found between gastric or diffuse-type cancer prognosis and other miRNAs. Our data demonstrate that specific miRNA SNPs are associated with gastric cancer susceptibility (miR-499A>G) and prognosis (miR-146aC>G and miR-499A>G) in the Korean population depending on gastric cancer type.
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http://dx.doi.org/10.1002/mc.21962DOI Listing
November 2013

Tumor necrosis factor-alpha promoter polymorphisms are associated with idiopathic primary ovarian insufficiency in Korean women.

Fertil Steril 2012 Nov 9;98(5):1260-5.e1-2. Epub 2012 Aug 9.

Department of Obstetrics and Gynecology and Fertility Center of CHA Bundang Medical Center, CHA University, Seoul, South Korea.

Objective: To investigate the possible association between primary ovarian insufficiency (POI) and TNF-α gene polymorphisms in Korean women.

Design: Case-control study.

Setting: An urban university-based hospital in South Korea.

Patient(s): A cohort of 135 Korean POI patients and 236 controls.

Intervention(s): None.

Main Outcome Measure(s): We analyzed TNF-α gene variants of all participants using the polymerase chain reaction-restriction fragment length polymorphism assay.

Result(s): The TNF-α -1031TC+CC, -238GA+AA, -1031TC+CC/-308GG, -1031TT/-308GA+AA, -1031TC+CC/-238GA+AA, and -308GG/-238GA+AA genotypes were significantly more frequent in POI patients than in controls. Among the haplotypes for the three TNF-α loci, the -1031C/-308G/-238A haplotype was more frequent in POI patients than in controls and conferred POI susceptibility. In analyses of two loci, the -1031T/-308A, -1031C/-308G, -1031C/-238A, and -308G/-238A haplotypes were more frequent in POI patients.

Conclusion(s): The TNF-α -1031C and -238A alleles had strong association with POI. The TNF-α -308A allele showed limited significance for POI risk with the presence of the -1031T allele. Our data suggest that the minor alleles of TNF-α promoter polymorphisms may increase POI risk in Korean women.
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http://dx.doi.org/10.1016/j.fertnstert.2012.07.1111DOI Listing
November 2012

Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G polymorphisms with risk of spontaneously aborted fetuses.

Am J Reprod Immunol 2012 Nov 13;68(5):408-17. Epub 2012 Aug 13.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

Problem: The miR-196a2T>C and miR-499A>G polymorphisms have been reported to be genetic risk factors for recurrent spontaneous abortion; however, that previous study focused on the genetic analyses of pregnant women rather than aborted fetuses. Because annexin A1 is a target of miR-196a2 and is related to anti-inflammation, miR-196a2 may be immunologically important. Moreover, miR-146a, miR-149, miR-196a2, and miR-499 have shown associations with immune responses.

Method Of Study: One hundred and eighty-two spontaneously aborted fetuses (SAFs) were <20 weeks of gestational age. The control subjects were 101 healthy children and 302 adults collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to identify the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G genotypes.

Results: Chromosomally normal SAFs had significantly different frequencies of the miR-196a2CC, miR-146aCC/miR-196a2CC, and miR-149TT/miR-196a2CC genotypes compared with control subjects.

Conclusions: miR-196a2CC, miR-146aCC/miR-196a2CC, and miR-149TT/miR-196a2CC in fetuses are possible risk factors for spontaneous abortion.
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http://dx.doi.org/10.1111/aji.12005DOI Listing
November 2012

Association of miR-146aC>G, miR-196a2T>C, and miR-499A>G polymorphisms with risk of premature ovarian failure in Korean women.

Reprod Sci 2013 Jan 7;20(1):60-8. Epub 2012 Aug 7.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

We investigated whether microRNA (miRNA) polymorphisms (miR-146aC>G, miR-196a2T>C, and miR-499A>G) confer risk of premature ovarian failure (POF) in Korean women. DNA samples from 136 patients with POF and 234 controls were genotyped for the 3 miRNA single-nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The miR-146aCG/miR-196a2TC combined genotype was less frequent in patients than in controls (P < .05), conferring less susceptibility. Using haplotype-based multifactor dimensionality reduction analysis, the C-C-A and G-T-A inferred haplotypes (miR-146a/miR-196a2/miR-499) were less frequent in patients, suggesting protective effects (P < .05 for each), whereas the C-T-A and G-C-A haplotypes were more frequent in patients (P < .05 for each). The C-T and G-C haplotypes (miR-146a/miR-196a2) were more frequent in patients, whereas the C-C and G-T haplotypes were less frequent in patients (P < .05 for each). However, none of the 3 miRNA polymorphisms alone was associated with POF risk. Our findings suggest that putative gene-gene interaction between miR-146 and miR-196a2 may be involved in POF development.
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http://dx.doi.org/10.1177/1933719112450341DOI Listing
January 2013

Association of methylenetetrahydrofolate reductase (MTHFR 677C>T) and thymidylate synthase (TSER and TS 1494del6) polymorphisms with premature ovarian failure in Korean women.

Menopause 2012 Nov;19(11):1260-6

Department of Biomedical Science, College of Life Science and Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Objective: The aim of our study was to investigate whether methylenetetrahydrofolate reductase (MTHFR) gene variant (MTHFR 677C>T) and thymidylate synthase (TS) gene variants (TS enhancer region [TSER] and TS 1494del6) confer a risk for premature ovarian failure (POF).

Methods: We genotyped 136 POF patients and 236 controls among Korean women for the three single nucleotide polymorphism sites using polymerase chain reaction restriction fragment length polymorphism analysis. Differences in the MTHFR 677C>T, TSER, and TS 1494del6 genotype frequencies between POF patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as a measure of the strength of the association between genotypes and POF.

Results: The MTHFR 677CT and CT + TT variant genotypes were more frequent in POF patients than in controls (OR, 2.249; 95% CI, 1.317-3.843; and OR, 2.132; 95% CI, 1.268-3.585, respectively). The combined genotype frequencies of MTHFR 677CT + TT/TSER 3R3R and 677CT + TT/TS 1494del6 del6/del6 were higher in patients than in controls (OR, 2.300; 95% CI, 1.219-4.337; and OR, 3.314; 95% CI, 1.623-6.767, respectively). The T-3R-del6 and T-2R-del6 (MTHFR 677C>T/TSER/TS 1494del6) haplotypes were more frequent in patients (OR, 1.450; 95% CI, 1.050-2.002; and OR, 2.911; 95% CI, 1.191-7.117, respectively), whereas the C-2R-del6 haplotype was less frequent in patients (OR, 0.372; 95% CI, 0.152-0.912). The T-del6 (MTHFR 677/TS 1494del6) haplotype frequency was higher among patients (OR, 1.653; 95% CI, 1.206-2.266), whereas the C-del6 haplotype frequency was lower among patients (OR, 0.700; 95% CI, 0.516-0.950). We did not find an association between TSER or TS 1494del6 polymorphisms and POF.

Conclusions: Our data suggest that the MTHFR 677T allele may increase the risk for POF, which could lead to the development of novel genetic markers for predicting the risk of POF in patients.
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http://dx.doi.org/10.1097/gme.0b013e3182556b08DOI Listing
November 2012

Association between kinase insert domain-containing receptor polymorphisms (-604T>C, 1192G>A, 1719A>T) and premature ovarian failure in Korean women.

Menopause 2012 Sep;19(9):1037-42

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

Objective: The aim of the study was to investigate whether the -604T>C, 1192G>A, and 1719A>T polymorphisms in the kinase insert domain-containing receptor (KDR) gene confer risk for premature ovarian failure (POF) in Korean women.

Methods: DNA samples from 133 POF patients and 230 controls were genotyped for the three KDR single nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis.

Results: The POF patients had significantly increased frequencies of the KDR -604TC and -604TC + CC genotypes (odds ratio [OR], 1.975; 95% CI, 1.219-3.201 and OR, 1.948; 95% CI, 1.221-3.109, respectively) and of the -604TC + CC/1192GG combined genotype (OR, 2.271; 95% CI, 1.359-3.795) and a decreased frequency of the 1192GA genotype (OR, 0.457; 95% CI, 0.231-0.905) compared with the controls. The genotype frequency of the 1719A>T polymorphism was not significantly different between the two groups. The frequencies of the KDR -604C/1192G/1719T, -604C/1192G, and -604C/1719T haplotypes (OR, 3.319; 95% CI, 1.564-7.041; OR, 2.083; 95% CI, 1.351-3.212; and OR, 1.979; 95% CI, 1.073-3.649, respectively) were significantly higher among POF patients than controls, whereas the -604T/1719T haplotype frequency (OR, 0.657; 95% CI, 0.472-0.915) was lower among POF patients.

Conclusions: Carriers of the KDR -604C variant allele (-604TC and -604TC + CC genotypes; -604TC + CC/1192GG combined genotype; -604C/1192G/1719T haplotype, -604C/1192G haplotype, -604C/1719T haplotype) are consistently more prevalent among POF patients than among controls, suggesting that the KDR -604C allele may increase the risk of POF development in Korean women.
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http://dx.doi.org/10.1097/gme.0b013e318248f2e8DOI Listing
September 2012

Solute Carrier Family 19, member 1 (SLC19A1) polymorphisms (-43T>C, 80G>A, and 696C>T), and haplotypes in idiopathic recurrent spontaneous abortion in a Korean population.

Reprod Sci 2012 May 16;19(5):513-9. Epub 2012 Feb 16.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.

The objective was to investigate the association between idiopathic recurrent spontaneous abortion (RSA) and 3 SLC19A1 polymorphisms (-43T>C, 80G>A, and 696C>T). DNA from 269 patients with RSA and 125 controls were genotyped for the 3 SLC19A1 single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism. Homocysteine and folate levels of 100 patients with RSA were available for analysis. The combination genotypes of SLC19A1 -43TC/80GG, -43TC/80AA, and -43CC/80GA; 80GA/696TT, 80AA/696CC; and -43TC/696CC were less frequent in patients with RSA compared to controls (P < .05 for each). The -43C/80A/696 T and -43T/80G/696C haplotypes were more frequent in patients than controls, whereas -43T/80A/696C, -43C/80A/696C, -43C/80G/696C, -43C/80G/696T, and -43T/80G/696T haplotypes were less frequent in patients (P < .05 for each). The -43T/80G and 80A/696T haplotypes were more frequent in patients, while -43T/80A, -43C/80G, 80A/696C, 80G/696T, and -43C/696C haplotypes occurred less frequently in patients (P < .05 for each). The associations between idiopathic RSA occurrence and SLC19A1 -43T>C/80G>A/696C>T polymorphisms were identified and can be developed as biomarkers for RSA risk.
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http://dx.doi.org/10.1177/1933719111426604DOI Listing
May 2012

Association study of microRNA polymorphisms with risk of idiopathic recurrent spontaneous abortion in Korean women.

Gene 2012 Feb 28;494(2):168-73. Epub 2011 Dec 28.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.

Aim: The aim of this study was to investigate the association of microRNA polymorphisms (miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G) in Korean patients with recurrent spontaneous abortion (RSA).

Methods: We conducted a case-control study of 564 Korean women: 330 patients with at least two unexplained consecutive pregnancy losses and 234 healthy controls with at least one live birth and no history of pregnancy loss.

Results: RSA patients exhibited significantly different frequencies of the miR-196a2CC (TT+TC vs. CC; adjusted odds ratio [AOR], 1.587; 95% confidence interval [CI], 1.042–2.417) and miR-499AG+GG genotypes (AOR, 1.587; 95% CI, 1.096–2.298) [corrected] compared with the control group. The combination of miR-196a2CC and miR-499AG+GG showed synergistic effects (AOR, 3.541; 95% CI, 1.645–7.624).

Conclusion: miR-196a2CC, miR-499AG+GG, and the miR-196a2CC/miR-499AG+GG combination are significantly associated with idiopathic RSA in Korean women.
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http://dx.doi.org/10.1016/j.gene.2011.12.026DOI Listing
February 2012

Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses.

Am J Reprod Immunol 2011 Dec 8;66(6):544-53. Epub 2011 Sep 8.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Problems: The VEGF-1154G>A polymorphism has been reported to be a genetic risk factor for recurrent spontaneous abortion in various studies; however, these studies have focused on genetic analyses of pregnant women rather than aborted fetuses. To evaluate and confirm the association between the VEGF-1154G>A polymorphism and spontaneous abortion, we focused on the relationship between four polymorphisms in the VEGF gene (-2578C>A, -1154G>A, -634G>C, and 936C>T) and spontaneously aborted fetuses (SAFs).

Method Of Study: The subjects included 118 SAFs at <20 weeks gestation and 380 normal controls consisting of children and adults. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.

Results: Spontaneously aborted fetuses exhibited significantly different frequencies of the -2578CA+AA/-634CC and -1154GA+AA/-634CC combined genotypes compared with control subjects. The frequency of the -2578A/-1154A/-634C/936C haplotype was significantly higher in SAFs.

Conclusions: VEGF genes -2578CA+AA/-634CC and -1154GA+AA/-634CC in the fetus are possible risk factors for spontaneous abortion.
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http://dx.doi.org/10.1111/j.1600-0897.2011.01067.xDOI Listing
December 2011

Identification of a unique library of complex, but ordered, arrays of repetitive elements in the human genome and implication of their potential involvement in pathobiology.

Exp Mol Pathol 2011 Jun 1;90(3):300-11. Epub 2011 Mar 1.

Burn Research, Shriners Hospitals for Children Northern California and Department of Surgery, University of California-Davis, 2425 Stockton Blvd., Sacramento, CA 95817, USA.

Approximately 2% of the human genome is reported to be occupied by genes. Various forms of repetitive elements (REs), both characterized and uncharacterized, are presumed to make up the vast majority of the rest of the genomes of human and other species. In conjunction with a comprehensive annotation of genes, information regarding components of genome biology, such as gene polymorphisms, non-coding RNAs, and certain REs, is found in human genome databases. However, the genome-wide profile of unique RE arrangements formed by different groups of REs has not been fully characterized yet. In this study, the entire human genome was subjected to an unbiased RE survey to establish a whole-genome profile of REs and their arrangements. Due to the limitation in query size within the bl2seq alignment program (National Center for Biotechnology Information [NCBI]) utilized for the RE survey, the entire NCBI reference human genome was fragmented into 6206 units of 0.5M nucleotides. A number of RE arrangements with varying complexities and patterns were identified throughout the genome. Each chromosome had unique profiles of RE arrangements and density, and high levels of RE density were measured near the centromere regions. Subsequently, 175 complex RE arrangements, which were selected throughout the genome, were subjected to a comparison analysis using five different human genome sequences. Interestingly, three of the five human genome databases shared the exactly same arrangement patterns and sequences for all 175 RE arrangement regions (a total of 12,765,625 nucleotides). The findings from this study demonstrate that a substantial fraction of REs in the human genome are clustered into various forms of ordered structures. Further investigations are needed to examine whether some of these ordered RE arrangements contribute to the human pathobiology as a functional genome unit.
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http://dx.doi.org/10.1016/j.yexmp.2011.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092023PMC
June 2011

Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

J Feline Med Surg 2006 Oct 13;8(5):357-60. Epub 2006 Jun 13.

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, 1114 Tupper Hall, Davis, CA 95616, USA.

An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.
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http://dx.doi.org/10.1016/j.jfms.2006.04.002DOI Listing
October 2006

Early-onset, autosomal recessive, progressive retinal atrophy in Persian cats.

Invest Ophthalmol Vis Sci 2005 May;46(5):1742-7

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.

Purpose: An early-onset retinal degenerative disease has been identified in Persian cats. This study genetically, clinically, and histologically characterized the disease. A breeding colony was established to assist with identification of the causative gene and to provide a resource for vision research.

Methods: Cats were produced from testcross breedings. Kittens underwent serial ophthalmic and neuro-ophthalmic examinations. Globes were harvested from age-matched affected, obligate carrier, and control cats and were evaluated by light microscopy. Fluorescein angiography assessed retinal and choroidal vasculature.

Results: Test breedings confirmed an autosomal recessive mode of inheritance. Rate and extent of disease progression were similar among individual affected cats. The earliest clinical signs (reduced pupillary light reflexes) were seen at 2 to 3 weeks of age. Retinal degeneration was virtually complete by 16 weeks of age. Histologic changes progressed rapidly and paralleled clinical findings. Histologic lesions were limited to the photoreceptors, outer plexiform layer, and retinal pigment epithelium in all but the terminal stages, when subtle changes were noted within the inner nuclear layer.

Conclusions: Characterized in this study was an autosomal recessive, early-onset, retinal degenerative disease in Persian cats that is likely to be more prevalent in this breed than previously suspected. This feline disease model may identify a new gene or provide biological insight into some forms of early-onset retinitis pigmentosa (RP) in humans and genetic retinal degenerations in other species. A breeding colony that will assist in the identification of the causative gene has been established and is available for studies in vision research.
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http://dx.doi.org/10.1167/iovs.04-1019DOI Listing
May 2005