Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Front Endocrinol (Lausanne). 2023 Jan 4;13:1056283. doi: 10.3389/fendo.2022.1056283. eCollection 2022.
Non-alcoholic fatty liver disease (NAFLD) is recognized to be closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, while previous studies have emphasized the important role of calcium homeostasis from the mitochondria-associated endoplasmic reticulum membrane (MAM) in the endoplasmic reticulum and mitochondria. This article will assess the association between genetic polymorphisms of Ca transport proteins and molecular chaperones in MAM and NAFLD risk.
A case-control study was conducted in a community of Nanjing, China during April to December 2020. 2701 subjects were enrolled and genotyped for 6 genetic variants in and genes. Logistic regression analysis was used to assess impact of these variants on NAFLD risk.
After adjusting for age, gender, total cholesterol and glucose, we identified that rs12009 variant genotypes (recessive model: OR= 0.801, 95% CI= 0.652-0.986, = 0.036), rs430397 variant genotypes (recessive model: OR= 0.546, 95% CI= 0.314-0.950, = 0.032), and rs11048570 variant genotypes (recessive model: OR= 0.673, 95% CI= 0.453-0.999, = 0.049) were associated with a reduced risk of NAFLD. Multivariate stepwise regression analysis indicated that gender, glucose, body mass index, triglycerides and favorable alleles were independent influencers of NAFLD (all < 0.05). The area under the receiver operating characteristic curve was 0.764 (95% CI= 0.745-0.783, < 0.001).
The variant genotypes of Ca transport-associated genes (rs12009 and rs430397) and (rs11048570) might contribute to the reduction of the NAFLD risk in Chinese Han population, which can provide new insight into NAFLD pathogenesis.
非酒精性脂肪性肝病(NAFLD)被认为与内质网应激和线粒体功能障碍密切相关,而先前的研究强调了线粒体相关内质网膜(MAM)中钙稳态对于内质网和线粒体的重要性。本文将评估 MAM 中钙转运蛋白和分子伴侣的遗传多态性与 NAFLD 风险之间的关联。
本研究于 2020 年 4 月至 12 月在中国南京的一个社区进行了病例对照研究。共纳入 2701 名受试者,并对 基因和 基因中的 6 个遗传变异进行了基因分型。采用 logistic 回归分析评估这些变异对 NAFLD 风险的影响。
在校正年龄、性别、总胆固醇和葡萄糖后,我们发现 rs12009 变异基因型(隐性模型:OR=0.801,95%CI=0.652-0.986,=0.036)、rs430397 变异基因型(隐性模型:OR=0.546,95%CI=0.314-0.950,=0.032)和 rs11048570 变异基因型(隐性模型:OR=0.673,95%CI=0.453-0.999,=0.049)与 NAFLD 风险降低相关。多元逐步回归分析表明,性别、葡萄糖、体重指数、甘油三酯和有利等位基因是 NAFLD 的独立影响因素(均<0.05)。受试者工作特征曲线下面积为 0.764(95%CI=0.745-0.783,<0.001)。
钙转运相关基因(rs12009 和 rs430397)和 (rs11048570)的变异基因型可能有助于降低汉族人群的 NAFLD 风险,这为 NAFLD 的发病机制提供了新的见解。