title: The relationship between five widely-evaluated variants in CDKN2A/B and CDKAL1 genes and the risk of type 2 diabetes: a meta-analysis.
abstract: The genes encoding two cyclin-dependent kinases-inhibitor-2A/B (CDKN2A/B) and 5 regulatory subunit-associated protein-like 1 (CDKAL1) have been investigated extensively in associations with type 2 diabetes; the results, however, are often irreproducible. We therefore sought to evaluate these associations by performing a meta-analysis on five widely-evaluated variants from the two genes. There were 38 studies (patients/controls: 51,940/52,234) for rs10811661, 16 studies (20,029/24,419) for rs564398 in CDKN2A/B gene, and 27 studies (28,383/47,635) for rs7756992, 26 studies (28,816/31,713) for rs7754840, 21 studies (29,260/38,400) for rs10946398 in CDKAL1 gene. Overall risk estimates for type 2 diabetes conferred by rs10811661-T, rs564398-A, rs7754840-C, rs7756992-G, and rs10946398-C alleles were 1.17 (95% CI: 1.10-1.23; P<0.0005; I(2)=83.9%), 1.1 (95% CI: 1.0-1.21; P=0.051; I(2)=88.3%), 1.24 (95% CI: 1.18-1.3; P<0.0005; I(2)=74.3%), 1.2 (95% CI: 1.11-1.3; P<0.0005; I(2)=92.0%), and 1.19 (95% CI: 1.1-1.29; P<0.0005; I(2)=90.8%), respectively. There was evident publication bias for rs564398 and rs7754840. Subgroup analyses by ethnicity showed remarkable divergences in risk estimate for rs564398 between Asians (odds ratio [OR]=1.01; 95% CI: 0.86-1.19; P=0.868) and Caucasians (OR=1.19; 95% CI: 1.03-1.35; P=0.012) (P<0.05). For all variants examined, the results of studies in retrospective design or with population-based controls were comparative with that of overall studies. In meta-regression analyses, age was found to exert a significant influence on the association between rs10811661 and type 2 diabetes (P=0.003), as well as between rs7754840 and gender (P=0.034). Taken together, our findings provide evidence for a significant contribution of CDKN2A/B gene rs10811661 and CDKAL1 gene rs7756992 and rs10946398 to type 2 diabetes.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Chaohao
authors.initials: C
authors.lastname: Gu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.forename: Shaoli
authors.initials: S
authors.lastname: Chu
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Lin
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
mesh_terms: D016022:Case-Control Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012189:Retrospective Studies; D012307:Risk Factors; D012359:tRNA Methyltransferases
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human
keywords: 5 regulatory subunit-associated protein-like 1; 95% CI; 95% confidence interval; CDKAL1; CDKN2A/B; CNKI; Chinese National Knowledge Infrastructure; Gene; Meta-analysis; OR; Type 2 diabetes; Variant; cyclin-dependent kinases-inhibitor-2A/B; odds ratio