title: Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with hypertension, alcohol intake, and cigarette smoking.
abstract: OBJECTIVE
  To evaluate whether an association between risk of any of the factors of hypertension, alcohol intake, and cigarette smoking and the risk of primary open-angle glaucoma (POAG) depended on nitric oxide synthase 3 (NOS3) gene variants.
  
  
  METHODS
  Two functional single-nucleotide polymorphisms (SNPs) (T-786C [rs2070744] and Glu298Asp [rs1799983]) and 2 tagging SNPs (rs7830 and rs3918188) were evaluated in nested case-control studies from the Nurses' Health Study (1980-2002) and the Health Professionals' Follow-up Study (1986-2002). Participants were 40 years of age or older and white, and were followed up biennially. We included 527 incident case patients with POAG and 1539 control participants, matched by cohort, age, and eye examination at the matched case patients' diagnosis dates. Cohort-specific relative risks were estimated using multivariable conditional logistic regression and were pooled using meta-analytic methods.
  
  
  RESULTS
  The association between hypertension and POAG depended on T-786C SNP variants. Compared with TT homozygotes without hypertension, the TT homozygotes with hypertension were at significantly higher risk of POAG (relative risk,1.45 [95% confidence interval, 1.01-2.08]); however, among carriers of the variant (C) allele, hypertension was not associated with POAG (P interaction = .007). Similarly, compared with CC homozygotes with the rs7830 tagging SNP who never smoked, CC homozygotes who were past or current smokers were at significantly higher risk of POAG (relative risk, 1.63 [95% confidence interval, 1.15-2.31]); however, among carriers of the variant allele (A), smoking was not associated with POAG (P interaction = .004). Interactions were not observed with alcohol intake.
  
  
  CONCLUSIONS
  The associations between hypertension and cigarette smoking in relation to POAG depended on NOS3 SNPs.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Haines
authors.forename: Wael
authors.initials: W
authors.lastname: Abdrabou
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
chemical_list: D004247:DNA; D052250:Nitric Oxide Synthase Type III