MC4R 基因附近的 rs17782313 多态性赋予肥胖和高血糖的高风险，而 PGC1α rs8192678 多态性与糖代谢紊乱弱相关：系统评价和荟萃分析。
The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis.
机构信息
Central Laboratory, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.
Department of Endocrinology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.
出版信息
Front Endocrinol (Lausanne). 2023 Aug 9;14:1210455. doi: 10.3389/fendo.2023.1210455. eCollection 2023.
BACKGROUND
The relationships of the rs17782313 polymorphism near melanocortin 4 receptor gene (MC4R) and the rs8192678 polymorphism in peroxisome proliferator-activated receptor gamma coactivator 1 alpha gene (PGC1α) with metabolic abnormalities have been explored in many populations around the world, but the findings were not all consistent and sometimes even a bit contradictory.
METHODS
Electronic databases including Medline, Scopus, Embase, Web of Science, CNKI and Google Scholar were checked for studies that met the inclusion criteria. Data were carefully extracted from eligible studies. Standardized mean differences (SMDs) were calculated by using a random-effects model to examine the differences in the indexes of obesity, glucometabolic disorder and dyslipidemia between the genotypes of the rs17782313 and rs8192678 polymorphisms. Cochran's Q-statistic test and Begg's test were employed to identify heterogeneity among studies and publication bias, respectively.
RESULTS
Fifty studies (58,716 subjects) and 51 studies (18,660 subjects) were respectively included in the pooled meta-analyses for the rs17782313 and rs8192678 polymorphisms. The C-allele carriers of the rs17782313 polymorphism had a higher average level of body mass index (SMD = 0.21 kg/m, 95% confidence interval [95% CI] = 0.12 to 0.29 kg/m, < 0.001), waist circumference (SMD = 0.14 cm, 95% CI = 0.06 to 0.23 cm, < 0.001) and blood glucose (SMD = 0.09 mg/dL, 95% CI = 0.02 to 0.16 mg/dL, = 0.01) than the TT homozygotes. Regarding the rs8192678 polymorphism, no significant associations with the indexes of obesity, glucometabolic disorder and dyslipidemia were detected. However, significant correlations between the rs8192678 polymorphism and multiple glucometabolic indexes were observed in subgroup analyses stratified by sex, age, ethnicity and health status.
CONCLUSION
The meta-analysis demonstrates that the C allele of the MC4R rs17782313 polymorphism confers a higher risk of obesity and hyperglycemia, and the PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder. These findings may partly explain the relationships between these variants and diabetes as well as cardiovascular disease.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022373543.
背景
在世界各地的许多人群中，已经研究了黑素皮质素 4 受体基因（MC4R）附近的 rs17782313 多态性和过氧化物酶体增殖物激活受体 γ 共激活因子 1α 基因（PGC1α）中的 rs8192678 多态性与代谢异常之间的关系，但研究结果并不完全一致，有时甚至有些矛盾。
方法
检索 Medline、Scopus、Embase、Web of Science、CNKI 和 Google Scholar 等电子数据库，以寻找符合纳入标准的研究。仔细从合格研究中提取数据。使用随机效应模型计算标准化均数差值（SMD），以检查 rs17782313 和 rs8192678 多态性的基因型在肥胖、糖代谢紊乱和血脂异常指标之间的差异。采用 Cochran's Q 统计量检验和 Begg 检验分别评估异质性和发表偏倚。
结果
分别有 50 项研究（58716 例受试者）和 51 项研究（18660 例受试者）纳入 rs17782313 和 rs8192678 多态性的汇总荟萃分析。rs17782313 多态性的 C 等位基因携带者的平均体重指数（SMD=0.21kg/m，95%置信区间[95%CI]为 0.12 至 0.29kg/m，<0.001）、腰围（SMD=0.14cm，95%CI 为 0.06 至 0.23cm，<0.001）和血糖（SMD=0.09mg/dL，95%CI 为 0.02 至 0.16mg/dL，=0.01）均高于 TT 纯合子。关于 rs8192678 多态性，未发现与肥胖、糖代谢紊乱和血脂异常指标有显著相关性。然而，在按性别、年龄、种族和健康状况进行分层的亚组分析中，发现 rs8192678 多态性与多种糖代谢指标之间存在显著相关性。
结论
荟萃分析表明，MC4R rs17782313 多态性的 C 等位基因增加了肥胖和高血糖的风险，而 PGC1α rs8192678 多态性与糖代谢紊乱呈弱相关。这些发现可能部分解释了这些变体与糖尿病和心血管疾病之间的关系。
系统综述注册
https://www.crd.york.ac.uk/prospero/，标识符 CRD42022373543。
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