Publications by authors named "Syeda Hafiza Benish Ali"

14 Publications

  • Page 1 of 1

Trends of climate change in the upper Indus basin region, Pakistan: implications for cryosphere.

Environ Monit Assess 2019 Jan 5;191(2):51. Epub 2019 Jan 5.

Department of Biosciences, COMSATS University Islamabad, Islamabad, 45550, Pakistan.

The Indus River, the lifeline of Pakistan's economy and its tributaries, derives most of water flow from the upper Indus basin comprised of Karakorum, Himalaya, and Hindu Kush mountain ranges, thus making this area important in climate change studies. We analyzed the records of climatic variables including temperature, precipitation, and relative humidity (RH) from two weather stations (Gilgit and Skardu) of upper Indus basin region from 1953 to 2006. To observe the trends of climate change, the selected time was divided into two temporal half periods consisting of 27 years each (1953-1979 and 1980-2006). The overall mean temperature (OMT) was decreased by - 0.137 °C in Gilgit, while an increase of 0.63 °C was observed in Skardu during the later period compared to the previous one. The mean minimum temperature (MMT) was found to decrease while mean maximum temperature (MXT) showed non-significant changes during the summer at both locations. However, there was an evidence of spring and winter warming at both locations due to increase in the MXT. The precipitation data showed large interannual variation at both locations. Significant increases in the morning relative humidity (RH) were observed during summer and autumn months at Skardu and throughout the year at Gilgit, while the evening RH increased during the same seasons at both stations. Significant increase in MXT and OMT during spring and winter months at higher elevation (Skardu) may have serious implications for the deposition and melting of seasonal snowpack with impacts on local livelihoods and river flow.
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http://dx.doi.org/10.1007/s10661-018-7184-3DOI Listing
January 2019

A 3' untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma.

Ann Hum Genet 2018 03 15;82(2):74-87. Epub 2017 Nov 15.

Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.79-7.06] and XPC rs2228001 (OR = 2.38, 95% CI = 1.43-3.94) with UBC. In stratified analysis with respect to smoking status, OGG1 rs2304277 and XPC rs2228001 exhibited increased risk in smokers [(rs2304277 OR = 4.96, 95% CI = 1.51-16.30) (rs2228001 OR = 2.19, 95% CI = 1.02-4.72)] as well as nonsmokers [(rs2304277 OR = 2.95, 95% CI = 1.26-6.90) (rs2228001 OR = 2.57, 95% CI = 1.31-5.04)]. These polymorphisms were also associated with both low-grade [(rs2304277 OR = 3.73, 95% CI = 1.72-8.09) (rs2228001 OR = 2.18, 95% CI = 1.21-3.92)] and high-grade tumors [(rs2304277 OR = 3.45, 95% CI = 1.52-7.80) (rs2228001 OR = 2.81, 95% CI = 1.48-5.33)] as well as with non-muscle-invasive bladder cancer [(rs2304277 OR = 4.03, 95% CI = 1.87-8.67) (rs2228001 OR = 2.14, 95% CI = 1.20-3.81)] and muscle-invasive bladder cancer [(rs2304277 OR = 3.06, 95%CI = 1.31-7.13) (rs2228001 OR = 2.95, 95%CI = 1.51-5.75)]. This is the first study on DNA repair gene polymorphisms and UBC in the Pakistani population. It identifies OGG1 rs2304277 and replicates XPC rs2228001 as significant modulators of UBC susceptibility.
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http://dx.doi.org/10.1111/ahg.12225DOI Listing
March 2018

Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population.

Fam Cancer 2017 Oct;16(4):577-594

Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan.

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non-smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.
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http://dx.doi.org/10.1007/s10689-017-9991-zDOI Listing
October 2017

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.

PLoS One 2015 14;10(12):e0144557. Epub 2015 Dec 14.

Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04-3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098-4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144557PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679138PMC
June 2016

Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

PLoS One 2015 16;10(3):e0119806. Epub 2015 Mar 16.

Department of Biosciences, Commission on Science and Technology for Sustainable Development in the South Institute of Information Technology, Islamabad, Pakistan; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Molecular Life sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.

Background: Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD).

Methods: We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.

Results: Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.

Conclusions: Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119806PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361598PMC
January 2016

Exome sequencing identifies three novel candidate genes implicated in intellectual disability.

PLoS One 2014 18;9(11):e112687. Epub 2014 Nov 18.

Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Islamabad, Pakistan; Department of Biochemistry, Al-Nafees Medical College & Hospital, Isra University, Islamabad, Pakistan.

Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K)-specific methyltransferase 2B (KMT2B), zinc finger protein 589 (ZNF589), as well as hedgehog acyltransferase (HHAT) with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112687PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236113PMC
July 2015

Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy.

Mol Vis 2013 21;19:710-7. Epub 2013 Mar 21.

Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Purpose: The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects.

Methods: A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism.

Results: We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33-0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2-0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37-1.19).

Conclusions: We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611930PMC
September 2013

Exome sequencing identifies a novel and a recurrent BBS1 mutation in Pakistani families with Bardet-Biedl syndrome.

Mol Vis 2013 21;19:644-53. Epub 2013 Mar 21.

Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Purpose: To determine the genetic cause of Bardet-Biedl syndrome (BBS) in two consanguineous Pakistani families.

Methods: Clinical characterization of the affected individuals in both families was performed with ophthalmic examination, electroretinography, electrocardiography, and liver and renal profiling. Seventeen genes are known to be associated with BBS, so exome sequencing was preferred over candidate gene sequencing. One affected individual from both families was selected for exome sequencing. Segregation of the identified variants was confirmed with Sanger sequencing.

Results: Retinitis pigmentosa, obesity, and learning difficulties were present in the affected individuals in both families. In family A, a sixth finger (polydactyly) of the proband's sister was removed by a surgical operation leaving a scar on the little finger. Polydactyly was also present in both affected individuals from family B. All diagnostic symptoms were characteristic of BBS in both families. In both affected individuals from family A, exome sequencing identified a novel homozygous mutation (c.47+1G>T) in BBS1 that inactivates the splice donor site at the end of exon 1. In family B, a previously reported mutation, c.442G>A; p.(Asp148Asn), was detected.

Conclusions: Exome sequencing is an efficient and cost-effective technique for identifying mutations in genetically heterogeneous diseases. In addition, intrafamilial phenotypic variability in family A argues for the modifying effect of other still unknown modifier alleles.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616519PMC
September 2013

Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia.

Gene 2013 Feb 21;515(2):416-20. Epub 2012 Dec 21.

Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad 45600, Pakistan.

Single nucleotide polymorphisms (SNPs) of non-coding RNA in the INK4 locus (ANRIL) have been found to be associated with myocardial infarction (MI). However, the effect of rs1333049:C>G in INK4 locus in familial hypercholesterolemia patients and on lipid profile of the patients has not been studied in Pakistan. We therefore investigated the association of SNP rs1333049:C>G with MI as well as familial hypercholesterolemia patients and also determined the effect of genotype on lipid levels in a northern Pakistani population. A case-control association study was performed in which 611 individuals (294 patients, 290 healthy controls and 27 patients from hypercholesterolemia families) were genotyped for rs1333049:C>G, using an Allele specific polymerase chain reaction. We found a significant association of rs1333049:C>G with MI (χ(2)=22.3, p<0.001). The frequency of risk genotype CC was significantly different from the healthy controls (p<0.001, χ(2)=22.3). The risk allele C was at a higher frequency in the MI patients as compared to the controls (odds ratio [OR]=1.55 (95% confidence interval [CI]=1.22-1.96), p<0.001). The logistic regression analysis for the genotype distribution resulted in strong association of risk allele C with MI under recessive model (OR=3.17 (95% CI=1.85-5.44) p<0.001). When the data were further analyzed along the lines of gender, a significant association with both males and females was observed. The pleiotropic role of rs1333049 was revealed further when CC genotype hypercholesterolemic individuals on statins were found to have a significantly lower TC, LDL-C and Tg levels as compared to the CG and GG individuals (p<0.05). The current study demonstrates a strong association of the ANRIL SNP (rs1333049) with MI as well as familial hypercholesterolemia patients in a northern Pakistani population and could be used as a useful genetic marker for the screening of MI in the general Pakistani population.
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http://dx.doi.org/10.1016/j.gene.2012.12.044DOI Listing
February 2013

Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families.

Mol Vis 2012 13;18:1558-71. Epub 2012 Jun 13.

Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Purpose: To identify the underlying genetic causes of fundus albipunctatus (FA), a rare form of congenital stationary night blindness that is characterized by the presence of white dots in the midperiphery of the retina and delayed dark adaptation, in Pakistan.

Methods: Two families with FA were identified by fundus examination, and genome-wide single nucleotide polymorphism genotyping was performed for two individuals from family A and six individuals from family B. Genotyping data were subsequently used to identify the identical homozygous regions present in the affected individuals of both families using the online homozygosity mapping tool Homozygosity Mapper. Candidate genes selected from the homozygous regions were sequenced.

Results: Three identical homozygous regions were identified in affected persons of family A (on chromosomes 8, 10, and 12), whereas a single shared homozygous region on chromosome 12 was found in family B. In both families, the homozygous region on chromosome 12 harbored the retinol dehydrogenase 5 (RDH5) gene, in which mutations are known to be causative of FA. RDH5 sequence analysis revealed a novel five base pair deletion, c.913_917delGTGCT (p.Val305Hisfs*29), in family A, and a novel missense mutation, c.758T>G (p.Met253Arg), in family B.

Conclusions: We identified two novel disease-causing RDH5 mutations in Pakistani families with FA, which will improve diagnosis and genetic counseling, and may even lead to treatment of this disease in these families.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380946PMC
November 2012

XRCC1 and XPD DNA repair gene polymorphisms: a potential risk factor for glaucoma in the Pakistani population.

Mol Vis 2011 4;17:1153-63. Epub 2011 May 4.

Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Purpose: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG).

Methods: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls.

Results: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ(2) = 12.1 [p < 0.005]), for both dominant (OR = 2.44 [95% CI = 1.33-4.47], p < 0.005) as well as recessive model (OR = 3.62 [95% CI = 1.45-9.01], p < 0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z = 3.00 [p < 0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.

Conclusions: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102023PMC
September 2011

A novel pathogenic nonsense triple-nucleotide mutation in the low-density lipoprotein receptor gene and its clinical correlation with familial hypercholesterolemia.

Genet Test Mol Biomarkers 2011 Sep 3;15(9):601-6. Epub 2011 Apr 3.

COMSATS Institute of Information Technology, Islamabad, Pakistan.

Aim: The aim of this study was to determine the genetic basis of familial hypercholesterolemia in a Pakistani family with a history of myocardial infarction and premature coronary artery disease.

Results: Direct sequencing of the low-density lipoprotein receptor gene resulted in the identification of a novel missense mutation c.264G>C (p.R88S) in exon 3 and a novel nonsense triple-nucleotide polymorphism (TNP) c.887-889GCA>AGC (p.C296X) in exon 6, the latter being probably the disease-causing mutation in this family. Both of these mutations were not present in the probands of 14 familial hypercholesterolemia families, 100 myocardial infarction patients, as well as 150 normolipidemic ethnically matched control individuals.

Conclusions: The identification of the novel nonsense TNP is the first report of a nonsense pathogenic TNP in low-density lipoprotein receptor or any other gene and only the fourth report of a pathogenic TNP of any type, which emphasizes the importance of screening for TNPs in patients and in familial studies that might otherwise be missed if only analyzed on single-nucleotide polymorphism arrays.
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http://dx.doi.org/10.1089/gtmb.2010.0184DOI Listing
September 2011

Identification of a recurrent insertion mutation in the LDLR gene in a Pakistani family with autosomal dominant hypercholesterolemia.

Mol Biol Rep 2010 Dec 10;37(8):3869-75. Epub 2010 Mar 10.

Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad, 45600, Pakistan.

Familial Hypercholesterolemia (FH) results in elevated levels of blood lipids including total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) with normal triglycerides (TG). This disease is one of the major contributors towards an early onset of coronary heart disease (CHD). The aim of the present study was to identify the genes responsible for causing FH in Pakistani population, for this purpose a large consanguineous FH family was selected for genetic analysis. Serum lipid levels, including TC, TG, LDL-C and high density lipoprotein cholesterol (HDL-C), were determined in patients and healthy controls. In order to find the causative mutation in this family, direct sequencing of the low density lipoprotein receptor (LDLR) gene was performed. In addition the part of the Apolipoprotein-B (APOB) gene containing the mutations R3500Q and R3500W was also sequenced. Affected individuals of the family were found to have raised TC and LDL-C levels. Sequencing revealed an insertion mutation (c.2416_2417InsG) in exon 17 of the LDLR gene in all the affected individuals of the family. Common FH causing APOB mutations were not present in this family. Heterozygous individuals had TC levels ranging from ~300-500 mg/dl and the only homozygous individual with typical xanthomas had TC levels exceeding 900 mg/dl. This is the first report of a known LDLR gene mutation causing FH in the Pakistani population. Despite a large heterogeneity of LDLR mutations there are still some common mutations which are responsible for FH throughout the world.
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http://dx.doi.org/10.1007/s11033-010-0043-0DOI Listing
December 2010

Association of eNOS and HSP70 gene polymorphisms with glaucoma in Pakistani cohorts.

Mol Vis 2010 Jan 11;16:18-25. Epub 2010 Jan 11.

Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

Purpose: To investigate the involvement of stress-regulating genes, endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG).

Methods: POAG and PCAG patients recruited from different areas of Pakistan were diagnosed on the basis of clinical history, raised intraocular pressure (IOP), cup-to-disc ratio (CDR) and visual field defects. Their blood was collected and genomic DNA was extracted from it, followed by PCR amplification and VNTR typing of the eNOS gene, while the HSP70 SNP was analyzed with PCR-RFLP. For both of the polymorphisms, the genotype distribution of the POAG and PCAG patients was compared with unaffected controls.

Results: HSP70 polymorphism was found to be significantly associated with PCAG (chi(2)=15.29 [p<0.001], OR=2.63 [95% CI=1.55-4.48]), with p<0.001 for the dominant model and OR=2.09 (95% CI=1.10-3.96) , with p<0.01 for the recessive model, but not with POAG (chi(2)=2.96 [p>0.05]). As opposed to this significant eNOS association, was seen with PCAG (chi(2)=6.33 [p<0.05], OR=2.09 [95% CI=1.12-3.89]), with p<0.01 for the dominant model, as well as with POAG (chi(2)=8.89 [p<0.05], OR=2.23 [95% CI=1.26-3.39]), with p<0.01 for dominant model. For the eNOS case, we found a significant association with the risk allele "a" for POAG patients (chi(2)=9.29 [p<0.01], OR=2.02 [95% CI=1.25-3.28, p=0.001]) and PCAG patients (chi(2)=7.59 [p<0.01], OR=1.99 [95% CI=1.18-3.37, p<0.01]). Similarly, in the HSP70 case, there was a significant association with the risk allele "C" for POAG patients (chi(2)=3.57 [p=0.05], OR=1.38 [95% CI=0.97-1.94, p<0.05]) and PCAG patients (chi(2)=18.32 (p<0.001), OR=2.16 [95% CI=1.49-3.13, p<0.001]).

Conclusions: The intron 4 polymorphism of eNOS is associated with POAG, as well as PCAG, while the G+190C polymorphism in HSP70 is associated with PCAG, but not with POAG in the Pakistani population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805420PMC
January 2010