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

Puneetpal Singh, Monica Singh, Rubanpal Khinda, Srishti Valecha, Nitin Kumar, Surinderpal Singh, Pawan K. Juneja, Taranpal Kaur and Sarabjit Mastana
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Puneetpal Singh: Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala 147002, India
Monica Singh: Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala 147002, India
Rubanpal Khinda: Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala 147002, India
Srishti Valecha: Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala 147002, India
Nitin Kumar: Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala 147002, India
Surinderpal Singh: Aggarwal Orthopedic Hospital, Ludhiana 141001, India
Pawan K. Juneja: Aggarwal Orthopedic Hospital, Ludhiana 141001, India
Taranpal Kaur: Amrit Sagar Hospital, Ferozepur 152001, India
Sarabjit Mastana: Human Genomics Lab., School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK

IJERPH, 2021, vol. 18, issue 3, 1-18

Abstract: 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)

Keywords: predictive models; endothelial dysfunction; osteoporosis; bone mineral density; SNP-SNP interactions; genetic models; haplotypes (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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