Association of CDKAL1 RS10946398 Gene Polymorphism with Susceptibility to Diabetes Mellitus Type 2: A Meta-Analysis

Abstract

Background. Diabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations. Aim. We aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations. Methods. We examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); $I^2$ was used to assess the heterogeneity (if $I^2<50$ %, the fixed-effects model was used; if $I^2\ge 50$ %, the random-effects model was used for data consolidation); correlation was judged by a forest map; potential publication bias was tested by the Egger test ( $p>0.05$ indicates that there is no publication bias). Results. Fourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant ( $p<0.01$ ) for dominant genetic model ( $\text{OR}=0.75$ , $95\%\text{CI}=0.64$ -0.88, $p=0.0003$ ). But the allelic effect model ( $\text{OR}=0.87$ , $95\%\text{CI}=0.75$ -1.02, $p=0.08$ ) and the recessive genetic model ( $\text{OR}=0.85$ , $95\%\text{CI}=0.66$ -1.10, $p=0.23$ ) were not statistically significant ( $p>0.01$ ). In the non-Asian population, the differences were statistically significant ( $p<0.01$ ) for the allelic effect model ( $\text{OR}=0.83$ , $95\%\text{CI}=0.77$ -0.88, $p<0.00001$ ), the dominant model ( $\text{OR}=0.79$ , $95\%\text{CI}=0.72$ -0.87, $p<0.00001$ ), and the recessive model ( $\text{OR}=0.78$ , $95\%\text{CI}=0.70$ -0.87, $p<0.0001$ ). Conclusion. In this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations.