Background: Genetic variants of the endothelial nitric oxide synthase (eNOS) gene have been reported to be associated with vascular disease. We hypothesized that G894T polymorphism might trigger many of the endocrine-metabolic cognitive changes related to aging.
Study design: One hundred and eighty subjects aged 5580+ years with moderately cognitive impairment (MCI) (MMSE<28) (lot 1), 140 age-matched subjects without cognitive impairment (MMSE>28) (lot 2) and 150 healthy subjects under 55 years were studied. The biochemical and hormonal profiles and eNOS gene G894T polymorphism evaluated.
Results: The frequencies of genotypes and alleles of G894T polymorphism according to age showed considerable differences among lots. The genotype and allele frequencies deviated from the HardyWeinberg equilibrium in subjects over age of 55 years (P<0.001 /lot 1 and P=0.04 /lot 2) compared with lot 3 under 55 years that was in HW equilibrium. The percentages of both G allele and GG genotype significantly decreased while T allele and TT genotype increased (OR=2.3; P<0.001 and OR=4.2; P<0.001) in lot 2 compared to lot 3. In the MCI group (lot 1) the tests for association showed risk allele G (OR=2.4; P=0.018); the percentages of both G allele and GG genotype significantly increased. GG genotype was significantly associated with cortisol, PRL, T3, T4, FT4 (OR=2.87; 95% CI=1.74.8; P<0.001) and more significantly with Glu, C-LDL, apoB, CRP and IGF1 (OR=4.6; 95% CI=2.58.3; P<0.001).
Conclusion: The findings suggest that there is a substantial difference in the distribution of gene G894T polymorphism between population under and over 55 years and that it is involved in aging process related to cognitive performance and endocrine changes. These results show an interaction between the G894T polymorphism and its phenotypes in conferring a higher susceptibility to the endocrine changes involved in healthy aging.