Genetic Scores of eNOS , ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women

The present study aimed to examine the participation and contribution of endothelial nitric oxide synthase ( eNOS ), angiotensin converting enzyme ( ACE ) and vascular endothelial growth factor ( VEGFA ) genes for the risk of endothelial dysfunction (ED)-associated osteoporosis risk in postmenopausal women of Punjab, India. Women with ED were categorized into women with osteoporosis (n = 346) and women without osteoporosis (n = 330). They were examined for selected SNPs within eNOS, ACE and VEGFA genes. Linear regression analysis revealed a positive association of ED with bone mineral densities (BMDs) at femoral neck (r 2 = 0.78, p < 0.001) and lumbar spine (r 2 = 0.24, p = 0.001) after Bonferroni correction. Three susceptibility haplotypes were exposed within eNOS (CTAAAT), ACE (ACDG) and VEGFA (GATA) genes. Bearers of CTAAAT (OR 2.43, p = 0.007), ACDG (OR 2.50, p = 0.002) and GATA (OR 2.10, p = 0.009) had substantial impact for osteoporosis after correcting the effects with traditional risk factors (TRD).With uncertainty measure ( R 2 h ) and Akaike information criterion (AIC), best fit models showed that CTAAAT manifested in multiplicative mode (β ± SE: 2.19 ± 0.86, p < 0.001), whereas ACDG (β ± SE: 1.73 ± 0.54, p = 0.001) and GATA (β ± SE: 3.07 ± 0.81, p < 0.001) expressed in dominant modes. Area under receiver operating characteristic curve using weighted risk scores (effect estimates) showed substantial strength for model comprising TRD + GATA (AUC = 0.8, p < 0.001) whereas, model comprising TRD + GATA + CTAAAT exhibited excellent ability to predict osteoporosis (AUC = 0.824, p < 0.001)