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Invest Ophthalmol Vis Sci. 2010 Feb;51(2):971-9. doi: 10.1167/iovs.09-4266. Epub 2009 Oct 8.

Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with sex and postmenopausal hormone use.

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  • 1Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA.

Abstract

PURPOSE:

To evaluate the association between the nitric oxide synthase gene (NOS3) variants and primary open-angle glaucoma (POAG).

METHODS:

Two functional single-nucleotide polymorphisms (SNPs) (T-786C: rs2070744; Glu298Asp: rs1799983) and three tagging SNPs (rs7830, rs3918188, and rs1800779) were evaluated in a nested case-control study from the Nurses' Health Study (1980-2002) and the Health Professionals' Follow-up Study (1986-2002). Participants were aged >or=40 years and Caucasian. Included were 527 incident cases and 1543 controls, matched by cohort, age, and eye examination at the matched cases' diagnosis dates. Cohort-specific relative risks (RR) were estimated by using multivariable conditional logistic regression and were pooled with meta-analysis.

RESULTS:

No NOS3 polymorphism was significantly associated with overall POAG. For high-tension POAG (HTPOAG), rs3918188 was significantly inversely associated among the women (AA versus CC genotype: RR = 0.48; 95% CI, 0.28-0.82) but not among the men (P-heterogeneity by sex = 0.02). The minor alleles of T -786C and rs1800779 showed positive association with high-tension POAG (P-trend < 0.02) in the women only, but P-heterogeneity was not significant. In the women, four of the five NOS3 SNPs showed significant interactions with postmenopausal hormone (PMH) use in relation to HTPOAG: for example, among the women with the TT genotype in T -786C, PMH use was inversely associated (RR = 0.41; 95% CI, 0.22-0.76), but among carriers of the minor allele, use of PMH was not associated.

CONCLUSIONS:

Interactions were observed between NOS3 SNPs and female sex and postmenopausal hormone use in the women in relation to HTPOAG. These findings should be confirmed in different racial/ethnic groups.

PMID:
19815736
[PubMed - indexed for MEDLINE]
PMCID:
PMC3094851
Free PMC Article

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