Division of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala, Punjab, India.
Human Genomics Lab, School of Sports, Exercise and Health Sciences, Loughborough University, Loughborough, UK.
Menopause. 2020 Jun;27(6):714-721. doi: 10.1097/GME.0000000000001514.
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.
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 single-nucleotide polymorphisms (SNPs) within the eNOS gene (rs2070744, rs1799983, rs1800780, rs3918181, rs891512, and rs1808593).
A moderate association between RHI and BMD at femoral neck (r = 0.213, P = 0.002) and lumbar spine (r = 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 (odds ratio [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 the eNOS gene which conferred 2.32 times higher chances of osteoporosis (OR 2.32, 95% confidence interval 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 the possibility of osteoporosis by a factor of 2.11 ± 0.63 (P < 0.001). RHI was significantly associated with susceptibility haplotype CTAAAT in a dose-dependent manner, whereby the severity of endothelial dysfunction increased significantly in women having two copies over women having one copy or no copy (β = 2.13, P < 0.001) of susceptibility haplotype.
A susceptibility haplotype CTAAAT within the eNOS gene is associated with double the possibility of endothelial dysfunction affiliated osteoporosis in postmenopausal women of Punjab, India.
探讨内皮型一氧化氮合酶（eNOS）基因遗传多态性与印度旁遮普邦绝经后妇女伴内皮功能障碍性骨质疏松症的关系。
本研究纳入了 456 名绝经后女性，根据是否存在骨质疏松症（n=220）将其分为两组。评估了骨密度（BMD）和反应性充血指数（RHI），并检测了 eNOS 基因内的 6 个单核苷酸多态性（SNP）（rs2070744、rs1799983、rs1800780、rs3918181、rs891512 和 rs1808593）。
RHI 与股骨颈（r=0.213，P=0.002）和腰椎（r=0.267，P<0.001）的 BMD 呈中度相关。SNP rs2070744 和 rs1799983 的次要等位基因 C 和 T 与两种显性（优势比[OR]2.13，P=0.017；OR 2.77，P=0.009）和共显性（OR 2.10，P=0.011；OR 2.45，P=0.007）模式下的骨质疏松症发生几率有关，而 SNP rs891512 的次要等位基因 A 在显性模型中具有边缘概率（OR 1.68，P=0.047）。在 eNOS 基因内观察到一个易感单倍型（CTAAAT），在调整混杂因素的影响后，该单倍型使骨质疏松症的发病几率增加了 2.32 倍（OR 2.32，95%置信区间 1.18-4.54，P=0.021）。遗传模型分析显示，每个易感单倍型的拷贝数增加了 2.11±0.63 倍（P<0.001）的骨质疏松症发病几率。RHI 与易感单倍型 CTAAAT 呈剂量依赖性相关，在携带两个易感单倍型的女性中，内皮功能障碍的严重程度明显高于携带一个或不携带易感单倍型的女性（β=2.13，P<0.001）。
在印度旁遮普邦的绝经后妇女中，eNOS 基因内的易感单倍型 CTAAAT 与内皮功能障碍相关骨质疏松症的发病几率增加了一倍。
