title: Association of eNOS and HSP70 gene polymorphisms with glaucoma in Pakistani cohorts.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Ayub
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ajmal
authors.forename: Sobia
authors.initials: S
authors.lastname: Shafique
authors.forename: Syeda Hafiza Benish
authors.initials: SH
authors.lastname: Ali
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Asifa
authors.initials: A
authors.lastname: Ahmed
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
mesh_terms: D020029:Base Pairing / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015812:Glaucoma, Angle-Closure / Q000201:enzymology / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000201:enzymology / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D018598:Minisatellite Repeats / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010154:Pakistan; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III