Objective: Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological studies on this topic, the results are still controversial. Methods: PubMed and Embase were screened for studies from their inception to 9 October 2016. The pooled odds ratio (OR) with the corresponding confidence intervals (CI) were used to measure the effect size for studies that reported the association under allelic, homozygous, and dominant models. Pre-specified characteristics were conducted in the subgroup analysis. Heterogeneity between subgroups was evaluated by meta-regression analysis. Results: Seven eligible studies involving 44,133 participants were included in our meta-analysis. Borderline significant association was observed between the LEPR gene polymorphism (rs1137101, rs1137100, rs6700896, and rs8179183) and the increased risk of CVD with considerable heterogeneity under the allelic model, and the overall pooled OR (95% CI) was 1.10 (0.99, 1.22). The LEPR gene variant rs6700896, 109G allele, and 109GG genotype were significantly associated with the increased risk of CVD. Furthermore, stratified group analysis revealed that the association was more pronounced for stroke. Race-differences might also cause the considerable heterogeneity and non-significant association. Conclusions: This is the first systematic review and meta-analysis to investigate the association between LEPR gene variants and CVD risk. Some LEPR gene variants were significantly associated with the increased risk of CVD. However, the present study is limited in its small number of included studies, considerable heterogeneity, and observational study design. Further research is still warranted to confirm the magnitude of the association.
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