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Genetic scores of ENOS, ACE and VEGFA genes are predictive of endothelial dysfunction associated osteoporosis in postmenopausal women

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journal contribution
posted on 22.03.2021, 11:34 by Puneetpal Singh, Monica Singh, Rubanpal Khinda, Srishti Valecha, Nitin Kumar, Surinderpal Singh, Pawan K Juneja, Taranpal Kaur, Sarabjit Mastana
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. 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 (r2 = 0.78, p < 0.001) and lumbar spine (r2 = 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 (R2h) 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).

Funding

Department of Science and Technology, Science and Engineering Research Board (DST-SERB), New Delhi (EMR/2016/0061)

History

School

  • Sport, Exercise and Health Sciences

Published in

International Journal of Environmental Research and Public Health

Volume

18

Issue

3

Publisher

MDPI

Version

VoR (Version of Record)

Rights holder

© The authors

Publisher statement

This is an Open Access Article. It is published by MDPI under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

Acceptance date

20/01/2021

Publication date

2021-01-22

Copyright date

2021

ISSN

1661-7827

eISSN

1660-4601

Language

en

Depositor

Dr Sarabjit Mastana. Deposit date: 17 March 2021

Article number

972