通过基因分析同型半胱氨酸与肥胖风险之间可能存在的关系：对38317名个体进行孟德尔随机化的荟萃分析

Plausible relationship between homocysteine and obesity risk via gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization.

作者信息

Fu Liwan, Li Ya-Nan, Luo Dongmei, Deng Shufang, Hu Yue-Qing

机构信息

State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.

Department of Information and Computing Science, School of Mathematics and Physics, Anhui University of Technology, Maanshan, Anhui, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2019 Jul 23;12:1201-1212. doi: 10.2147/DMSO.S205379. eCollection 2019.

OBJECTIVE

Numerous studies have explored the role of methylenetetrahydrofolate reductase gene () C677T polymorphism and homocysteine (Hcy) concentration in obesity, but the results are inconsistent. Hence, we performed a meta-analysis implementing Mendelian randomization approach to test the assumption that the increased Hcy concentration is plausibly related to the elevated risk of obesity.

METHODS

Eligible studies were selected based on several inclusion and exclusion criteria. Correlations between C677T and obesity risk, C677T and Hcy concentration in obesity, Hcy concentration, and obesity were estimated by ORs, effect size and standard mean difference with their corresponding 95% CIs, respectively. Furthermore, Mendelian randomization analysis was performed to estimate the relationship between Hcy level and obesity.

RESULTS

Consequently, this meta-analysis implemented with Mendelian randomization approach was conducted among 8,622 cases and 29,695 controls. The results indicated that C677T is associated with an increased risk of obesity (for T vs C: OR=1.06, 95% CI=1.02-1.10; for TT vs CC: OR=1.13, 95% CI=1.03-1.24). Moreover, in obese subjects, the pooled Hcy concentration in individuals of TT genotype was 2.91 mmol/L (95% CI: 0.27-5.55) higher than that in individuals of CC genotype. Furthermore, the pooled Hcy concentration in subjects with obesity was 0.74 mmol/L (95% CI: 0.36-1.12) higher than that in controls. The evaluated plausible OR associated with obesity was 1.23 for 5 μmol/L Hcy level increase.

CONCLUSIONS

Through this meta-analysis, we emphasize a strong relationship between Hcy level and obesity by virtue of C677T polymorphism.

目的

众多研究探讨了亚甲基四氢叶酸还原酶基因（）C677T多态性及同型半胱氨酸（Hcy）浓度在肥胖症中的作用，但结果并不一致。因此，我们采用孟德尔随机化方法进行了一项荟萃分析，以检验Hcy浓度升高可能与肥胖风险增加相关这一假设。

方法

根据多项纳入和排除标准选择符合条件的研究。分别通过比值比（OR）、效应量和标准均数差及其相应的95%置信区间（CI）来估计C677T与肥胖风险、肥胖症中C677T与Hcy浓度、Hcy浓度与肥胖症之间的相关性。此外，进行孟德尔随机化分析以估计Hcy水平与肥胖症之间的关系。

结果

因此，本采用孟德尔随机化方法的荟萃分析在8622例病例和29695例对照中进行。结果表明，C677T与肥胖风险增加相关（T vs C：OR = 1.06，95% CI = 1.02 - 1.10；TT vs CC：OR = 1.13，95% CI = 1.03 - 1.24）。此外，在肥胖受试者中，TT基因型个体的合并Hcy浓度比CC基因型个体高2.91 mmol/L（95% CI：0.27 - 5.55）。此外，肥胖受试者的合并Hcy浓度比对照组高0.74 mmol/L（95% CI：0.36 - 1.12）。Hcy水平每升高5 μmol/L，与肥胖相关的评估似然OR为1.23。