Endocrine Abstracts

Introduction: Differences in the prevalence and prognosis of cardiovascular disease have been linked with gender specific risk factors as well as the differential impact of sex hormones. Moreover, specific genetic polymorphisms may increase further the risk of cardiovascular disease development. Polymorphisms of genes encoding the NADPH/NADPH oxidase system and the endothelial nitric oxide synthase (eNOS) have been associated with atherosclerosis in the general population, but their significance in reproductively active women remains underexplored. We aimed to investigate the potential association between the C242T polymorphism of the CYBA gene and the G894T polymorphism of the NOS3 gene with the development of subclinical atherosclerosis in young women.

Methods: This cross-sectional study recruited a total of 70 healthy, normally ovulating, reproductively active women. Fasting venous blood samples were obtained for genotyping, using real-time PCR, as well as for hormonal and biochemical assessment. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD) and carotid-femoral pulse-wave velocity (PWV).

Results: The prevalence of genotypes was as follows: for the C242T polymorphism, wild type in 38.6% (27/70), heterozygote in 31.4% (22/70), and homozygote in 30.0% (21/70); for the G894T polymorphism, wild type in 44.3% (31/70), heterozygote in 54.3% (38/70), and homozygote in 1.4% (1/70). Presence of the heterozygous genotype of the C242T polymorphism associated significantly with internal carotid IMT (b-coefficient = − 0.119, P = 0.011) and combined-IMT (b-coefficient = − 0.061, P = 0.015), after adjustment for traditional risk factors in the multivariable analysis. Values of FMD were associated with systolic blood pressure, lipids and the presence of the heterozygous C242T polymorphism (FMD, b-coefficient – 1.604, P = 0.034). In the univariate analysis, carriers of the G894T NOS3 polymorphic variant had had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; P = 0.048 and P = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis.

Conclusion: The CYBA C242T polymorphism is associated with subclinical atherosclerosis of the carotid arteries as well as with endothelial function, in healthy reproductively active women. The NOS3 G894T polymorphic variant also associated with indices of subclinical atherosclerosis, however this association is possibly mediated by the effect of traditional cardiovascular risk factors. The significance of these findings in the clinical setting remains to be elucidated by larger prospective studies.