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

• Main Authors: Puneetpal Singh, Monica Singh, Rubanpal Khinda, Srishti Valecha, Nitin Kumar, Surinderpal Singh, Pawan K. Juneja, Taranpal Kaur, Sarabjit Mastana
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: predictive models; endothelial dysfunction; osteoporosis; bone mineral density; SNP-SNP interactions; genetic models
• Online Access: https://www.mdpi.com/1660-4601/18/3/972
• ISSN: 1661-7827; 1660-4601

The present study aimed to examine the participation and contribution of endothelial nitric oxide synthase (<i>eNOS</i>), angiotensin converting enzyme (<i>ACE</i>) and vascular endothelial growth factor (<i>VEGFA</i>) 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 <i>eNOS, ACE</i> and <i>VEGFA </i>genes. Linear regression analysis revealed a positive association of ED with bone mineral densities (BMDs) at femoral neck (r²= 0.78, <i>p</i> < 0.001) and lumbar spine (r²= 0.24, <i>p</i> = 0.001) after Bonferroni correction. Three susceptibility haplotypes were exposed within <i>eNOS</i> (CTAAAT), <i>ACE </i>(ACDG) and <i>VEGFA</i> (GATA) genes. Bearers of CTAAAT (OR 2.43, <i>p</i> = 0.007), ACDG (OR 2.50, <i>p</i> = 0.002) and GATA (OR 2.10, <i>p</i> = 0.009) had substantial impact for osteoporosis after correcting the effects with traditional risk factors (TRD).With uncertainty measure (<i>R</i>²_h) and Akaike information criterion (AIC), best fit models showed that CTAAAT manifested in multiplicative mode (β ± SE: 2.19 ± 0.86, <i>p</i> < 0.001), whereas ACDG (β ± SE: 1.73 ± 0.54, <i>p</i> = 0.001) and GATA (β ± SE: 3.07 ± 0.81, <i>p</i> < 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, <i>p</i> < 0.001) whereas, model comprising TRD + GATA + CTAAAT exhibited excellent ability to predict osteoporosis (AUC = 0.824, <i>p</i> < 0.001)