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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 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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