Association between KCNJ11 E23K polymorphism and the risk of type 2 diabetes mellitus: A global meta-analysis

Potassium inwardly rectifying channel, subfamily J member 11(KCNJ11) is considered to be a potential susceptible gene of type 2 diabetes mellitus (T2DM), and the association between KCNJ11 E23K polymorphism and T2DM risk is still controversial worldwide. This meta-analysis was performed to assess the association more accurately between KCNJ11 E23K polymorphism and T2DM risk.

The up-to-data meta-analysis was conducted based on studies selected from eight databases (PubMed, Web of Science, Medline, Scopus, Embase, CNKI, WanFang, and Vip). Five gene models were included in our study: allele model (K-allele vs. E-allele), heterozygous model (EK vs. EE), homozygous model (KK vs. EE), dominant genetic model (EK + KK vs. EE), and recessive genetic model (EK + EE vs. KK). Association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI), publication bias was evaluated by Begg's funnel plot and Egger's test, sensitivity analysis and trial sequential analysis (TSA) were used to evaluate the stability of the results.

According to the inclusion and exclusion criteria, 31 eligible articles were finally selected in our meta-analysis, including 8754 T2DM cases and 7587 controls. We found that allelic model (OR = 1.25, 95%CI: 1.15-1.35, P < 0.01), heterozygous model (OR = 1.31, 95% CI: 1.18-1.44, P < 0.01), homozygous model (OR = 1.48, 95% CI: 1.24-1.76, P < 0.01), and dominant genetic model (OR = 1.35, 95% CI: 1.22-1.50, P < 0.01) were significantly associated with increased risk of T2DM, but recessive genetic model (OR = 0.78, 95% CI: 0.67-0.91, P < 0.01) was considered as a protective factor for T2DM. No significant evidence of publication bias was found.

Our meta-analysis confirms the association between KCNJ11 E23K polymorphism and the risk of T2DM, highlighting that gene-gene interaction and gene-environment interaction should be investigated in future.