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Investigation of eNOS gene polymorphism exposes a genetic association between endothelial dysfunction and osteoporosis in postmenopausal women

journal contribution
posted on 13.01.2020, 13:39 by Puneetpal Singh, Monica Singh, Srishti Valecha, Rubanpal Kinda, Nitin Kumar, Sarabjit Mastana, Surinderpal Singh, Pawan K Juneja, Taranpal Kaur
Objectives:To investigate the association of genetic polymorphisms of endothelial nitric oxide synthase (eNOS) gene with endothelial dysfunction associated osteoporosis in postmenopausal women of Punjab, India.
Methods:The study involved 456 postmenopausal women having endothelial dysfunction categorized according to women with (n=236) and without osteoporosis (n=220). Bone mineral density (BMD) and reactive hyperemia index (RHI) were evaluated together with six SNPs within the eNOS gene (rs2070744, rs1799983, rs1800780, rs3918181, rs891512 and rs1808593).
Results:A moderate association between RHI and BMD at femoral neck (r2=0.213, P=0.002) and lumbar spine (r2=0.267, P<0.001) was observed. Minor alleles C and T of SNPs;rs2070744 and rs1799983 were associated with chances of osteoporosis in both co- dominant (OR 2.13, P=0.017,OR 2.77, P=0.009) and dominant (OR 2.10, P=0.011, OR 2.45, P=0.007) modes whereas, minor allele A of SNP rs891512 showed marginal probability in dominant model (OR 1.68, P=0.047). A susceptibility haplotype (CTAAAT) was observed within eNOS gene which conferred 2.32 times higher chances of osteoporosis (OR 2.32, 95%CI 1.18-4.54, P=0.021) after adjusting for the effect of confounders. Genetic model analysis revealed that each copy of susceptibility haplotype increased possibility of osteoporosis by factor of 2.11±0.63 (P<0.001). RHI was significantly associated with susceptibility haplotype CTAAAT in dose dependent manner, whereby the severity of endothelial dysfunction increased significantly in women having 2 copies over women having 1 copy or no copy (β=2.13, P<0.001) of susceptibility haplotype.
Conclusion:A susceptibility haplotype CTAAAT within eNOS gene is associated with double the possibility of endothelial dysfunction affiliated osteoporosis in postmenopausal women of Punjab, India.

Funding

Project number EMR/2016/006161 sanctioned to Puneetpal Singh by Department of Science and Technology-Science and Engineering Research Board, New Delhi.

History

School

  • Sport, Exercise and Health Sciences

Published in

Menopause: The Journal of the North American Menopause Society

Volume

27

Issue

6

Pages

714 - 721

Publisher

Lippincott, Williams & Wilkins

Version

AM (Accepted Manuscript)

Rights holder

© The North American Menopause Society.

Publisher statement

This is a non-final version of an article published in final form in Menopause: The Journal of the North American Menopause Society, 27 (6), pp.714-721, doi:10.1097/GME.0000000000001514.

Acceptance date

08/01/2020

Publication date

2020-03-16

Copyright date

2020

ISSN

1072-3714

eISSN

1530-0374

Language

en

Depositor

Dr Sarabjit Mastana. Deposit date: 13 January 2020

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