Association of KCNJ11 gene polymorphisms with the risk of type 2 diabetes mellitus: A PRISMA-driven systematic review of 30,373 individuals

Background: A large number of studies have investigated the relationship between the polymorphism of potassium ion inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) and the susceptibility to type 2 diabetes mellitus (T2DM), but the results are still controversial. Objective: We studied three gene polymorphisms:rs5219, rs5218, rs5215, and analyzed the allele genetic model, dominant genetic model and recessive genetic model respectively to research the association of the KCNJ11 gene polymorphism with T2D risk. Eligibility criteria: Relevant information of selected articles were independently extracted by 2 reviewers following a predetermined standardized data extraction form. Data sources: We researched databases through PubMed, Web of Science so as to identify all relevant articles published from January 2005 to October 2019. Review appraisl:We used a 95% confidence interval (CI) of the odds ratio (OR) to evaluate the strength of association between these three polymorphisms and T2DM. Z test was used to determine the significance of OR. Q test and I
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test were used to evaluate inter-study heterogeneity. Eeggr’s test and Begg’s test were used to evaluate publication bias. Results:28 relevant studies which involved 30,373 patients, including 16,155 cases and 14,218 groups were included. The results showed that KCNJ11 rs5219 (OR: 1.15, 95%Cl: 1.07-1.23, P = 0.000)and rs5215 (OR: 1.48, 95%CI: 1.10-1.99, P=0.009)were strongly associated with T2DM, while there was no significant association between rs5218 (OR: 0.85, 95%CI: 0.75-0.96, P = 0.008)and T2DM. Dominant genetic model and recessive genetic model were consistent with these results. Besides, subgroup analysis (Caucasian, East Asian, North African and Others) and sensitivity analysis were consistent with the above results as well. Limitations: Due to the quantity and quality of literature, we only analyzed three polymorphisms (rs5219 rs5218 rs5215), while the others could not be explained because of insufficient literature. Conclusions: This meta-analysis confirmed that KCNJ11 rs5219 and rs5215 polymorphism (SNPs) were significantly associated with the risk of T2DM.