Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women,International Journal of Environmental Research and Public Health

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Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women
International Journal of Environmental Research and Public Health Pub Date : 2021-01-22 , DOI: 10.3390/ijerph18030972
Puneetpal Singh ₁ , Monica Singh ₁ , Rubanpal Khinda ₁ , Srishti Valecha ₁ , Nitin Kumar ₁ , Surinderpal Singh ₂ , Pawan K Juneja ₂ , Taranpal Kaur ₃ , Sarabjit Mastana ₄

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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 (R²_h) 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)

中文翻译：

eNOS、ACE 和 VEGFA 基因的遗传评分可预测绝经后妇女内皮功能障碍相关的骨质疏松症

本研究旨在检查内皮一氧化氮合酶 ( eNOS )、血管紧张素转换酶 ( ACE ) 和血管内皮生长因子 ( VEGFA ) 基因对绝经后妇女发生内皮功能障碍 (ED) 相关骨质疏松症风险的影响和贡献。印度旁遮普邦。患有 ED 的女性被分为患有骨质疏松症的女性 (n = 346) 和没有骨质疏松症的女性 (n = 330)。检查了它们在eNOS、ACE和VEGFA基因中的选定 SNP。线性回归分析显示 ED 与股骨颈 (r ² = 0.78, p < 0.001) 和腰椎 (r² = 0.24, p = 0.001) 在 Bonferroni 校正后。在eNOS (CTAAAT)、ACE (ACDG) 和VEGFA (GATA) 基因中暴露了三种易感性单倍型。CTAAAT (OR 2.43, p = 0.007)、ACDG (OR 2.50, p = 0.002) 和 GATA (OR 2.10, p = 0.009) 在用传统危险因素 (TRD) 校正影响后对骨质疏松症有重大影响。测量 ( R ²_h ) 和 Akaike 信息准则 (AIC)，最佳拟合模型显示 CTAAAT 表现为乘法模式 (β ± SE: 2.19 ± 0.86, p < 0.001)，而 ACDG (β ± SE: 1.73 ± 0.54,p = 0.001) 和 GATA (β ± SE: 3.07 ± 0.81, p < 0.001) 以主导模式表示。使用加权风险评分（效果估计）的受试者工作特征曲线下面积显示包含 TRD + GATA 的模型具有显着优势（AUC = 0.8，p < 0.001），而包含 TRD + GATA + CTAAAT 的模型表现出出色的预测骨质疏松症的能力（AUC = 0.824, p < 0.001)

更新日期：2021-01-22

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