LEPR基因Q223R和K109R多态性与2型糖尿病风险相关性的荟萃分析。
A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk.
作者信息
Yang Yunzhong, Niu Tianhua
机构信息
Department of Global Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States of America.
Department of Biochemistry and Molecular Biology, Tulane University School Medicine, New Orleans, LA, United States of America.
出版信息
PLoS One. 2018 Jan 2;13(1):e0189366. doi: 10.1371/journal.pone.0189366. eCollection 2018.
BACKGROUND
Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility.
METHODS
A comprehensive search was conducted to identify all eligible case-control studies for examining the associations of LEPR single nucleotide polymorphisms (SNPs) Q223R (rs1137101) and K109R (rs1137100) with T2D risk. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to measure the magnitudes of association.
RESULTS
For Q223R, 13 studies (11 articles) consisting of a total of 4030 cases and 2844 controls, and for K109R 7 studies (7 articles) consisting of 3319 cases and 2465 controls were available. Under an allele model, Q223R was not significantly associated with T2D risk (OR = 1.09, 95% CI: 0.80-1.48, P-value = 0.5989), which was consistent with results obtained under four genotypic models (ranges: ORs 1.08-1.20, 95% CIs: 0.58-2.02 to 0.64-2.26; P-values, 0.3650-0.8177, which all exceeded multiplicity-adjusted α = 0.05/5 = 0.01). In addition, no significant association was found between K109R and T2D risk based on either an allele model (OR = 0.93, 95% CI: 0.85-1.03, P-value = 0.1868) or four genotypic models (ranges: ORs 0.81-0.99, 95% CIs: 0.67-0.86 to 0.97-1.26, P-values, 0.0207-0.8804 which all exceeded multiplicity-adjusted α of 0.01). The magnitudes of association for these two SNPs were not dramatically changed in subgroup analyses by ethnicity or sensitivity analyses. Funnel plot inspections as well as Begg and Mazumdar adjusted rank correlation test and Egger linear regression test did not reveal significant publication biases in main and subgroup analyses. Bioinformatics analysis predicted that both missense SNPs were functionally neutral and benign.
CONCLUSIONS
The present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk.
背景
瘦素受体（LEPR）在体重控制、能量代谢和胰岛素敏感性方面发挥着关键作用。进行了各种基因关联研究，以评估LEPR基因变异与2型糖尿病（T2D）易感性之间的关联。
方法
进行全面检索，以确定所有符合条件的病例对照研究，用于检验LEPR单核苷酸多态性（SNP）Q223R（rs1137101）和K109R（rs1137100）与T2D风险的关联。比值比（OR）和相应的95%置信区间（CI）用于衡量关联强度。
结果
对于Q223R，有13项研究（11篇文章），共包括4030例病例和2844例对照；对于K109R，有7项研究（7篇文章），共包括3319例病例和2465例对照。在等位基因模型下，Q223R与T2D风险无显著关联（OR = 1.09，95% CI：0.80 - 1.48，P值 = 0.5989），这与在四种基因型模型下获得的结果一致（范围：OR为1.08 - 1.20，95% CI：0.58 - 2.02至0.64 - 2.26；P值，0.3650 - 0.8177，均超过多重性调整后的α = 0.05/5 = 0.01）。此外，基于等位基因模型（OR = 0.93，95% CI：0.85 - 1.03，P值 = 0.1868）或四种基因型模型（范围：OR为0.81 - 0.99，95% CI：0.67 - 0.86至0.97 - 1.26，P值，0.0207 - 0.8804，均超过多重性调整后的α = 0.01），未发现K109R与T2D风险之间存在显著关联。在按种族进行的亚组分析或敏感性分析中，这两个SNP的关联强度没有显著变化。漏斗图检查以及Begg和Mazumdar调整秩相关检验和Egger线性回归检验在主要和亚组分析中均未发现显著的发表偏倚。生物信息学分析预测，这两个错义SNP在功能上是中性的且为良性。
结论
本荟萃分析未检测到LEPR Q223R和K109R多态性与T2D风险之间存在显著的基因关联。
Zotero 插件