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A susceptibility haplotype within the endothelial nitric oxide synthase gene influences bone mineral density in hypertensive women

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Abstract

The influence of the coordinated effect of various single-nucleotide polymorphisms (SNPs) within the endothelial nitric oxide synthase (eNOS) gene on the risk of osteoporosis in hypertension has remained undetermined. Four pertinent SNPs of the eNOS gene, rs2070774, rs1799983, rs1800780 and rs3918181, were examined for the risk of osteoporosis in 313 hypertensive postmenopausal women in Northwest India. All the hypertensive women were verified with dual energy X-ray absorptiometry and categorized as 150 with osteoporosis and 163 without osteoporosis. The minor allele (T) of rs1799983 exerts a statistically significant risk for osteoporosis both in dominant [odds ratio (OR) 3.71, 95 % confidence interval (CI) 2.12–6.49, P < 0.001] and recessive mode (OR 5.75, 95 % CI 1.24–26.69, P = 0.036) after Bonferroni correction. Bone mineral density (BMD) values (corrected for the effects of risk variables) according to eNOS SNP genotypes revealed a significant association with rs1799983 at both the lumbar spine (P = 0.001) and femoral neck (P = 0.023). Risk association analyses revealed a susceptibility haplotype TTAG which influences the risk of osteoporosis (OR 2.02, 95 % CI 1.05–3.39, P = 0.042) in hypertension after adjusting for the effects of risk factors. Furthermore, this haplotype was significantly associated with BMD at the lumbar spine (P = 0.029) and femoral neck (P = 0.021) in a dose-dependent manner. The results suggest that possession of the TTAG haplotype of the eNOS gene may increase the risk of osteoporosis two-fold in hypertensive postmenopausal women in Northwest India.

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Acknowledgments

The financial support of the DST project (SR/WOS-A/LS-387/2011) to MS is highly acknowledged.

Conflict of interest

All the authors have no conflict of interest.

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Authors and Affiliations

  1. Molecular Genetics Laboratory, Department of Human Genetics, Punjabi University, Patiala, 147002, Punjab, India

    Monica Singh & Puneetpal Singh

  2. Aggarwal Orthopedic Hospital, Ludhiana, India

    Surinder Singh & Pawan Kumar Juneja

  3. Amrit Sagar Hospital, Ferozepur, India

    Taranpal Kaur

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  1. Monica Singh
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  2. Puneetpal Singh
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  3. Surinder Singh
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  4. Pawan Kumar Juneja
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  5. Taranpal Kaur
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Correspondence to Puneetpal Singh.

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Singh, M., Singh, P., Singh, S. et al. A susceptibility haplotype within the endothelial nitric oxide synthase gene influences bone mineral density in hypertensive women. J Bone Miner Metab 32, 580–587 (2014). https://doi.org/10.1007/s00774-013-0533-y

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  • DOI: https://doi.org/10.1007/s00774-013-0533-y

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