Dataset Information

Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: a meta-analysis of 70141 subjects.

ABSTRACT: The reported association of the CDKAL1 rs7754840 G/C gene polymorphism with T2DM susceptibility remains controversial. In this study, this association was further investigated using a meta-analysis of 33,149 patients and 36,992 controls from 32 independent studies. The random-effect models were used in order to evaluate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). A significant relationship between the CDKAL1 rs7754840 G/C gene polymorphism and T2DM was observed under allelic (OR: 1.37, 95% CI: 1.22, 1.55, P < 0.001), recessive (OR: 1.58, 95% CI: 1.20-2.08, P < 0.001), dominant (OR: 1.13, 95% CI: 1.21-1.33, P = 0.01), and homozygous (OR: 1.27, 95% CI: 1.21-1.33, P < 0.001), and heterozygous (OR: 0.83, 95% CI: 0.75-0.93, P < 0.001). Overall, the CDKAL1 rs7754840 G/C gene polymorphism was found to be significantly associated with an increased T2DM risk; the C allele of the CDKAL1 rs7754840 G/C gene polymorphism may confer susceptibility to T2DM.

SUBMITTER: Tuerxunyiming M

PROVIDER: S-EPMC4694230 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: a meta-analysis of 70141 subjects.

Tuerxunyiming Muhadasi M Mohemaiti Patamu P Wufuer Hamulati H Tuheti Awaguli A

International journal of clinical and experimental medicine 20151015 10

The reported association of the CDKAL1 rs7754840 G/C gene polymorphism with T2DM susceptibility remains controversial. In this study, this association was further investigated using a meta-analysis of 33,149 patients and 36,992 controls from 32 independent studies. The random-effect models were used in order to evaluate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). A significant relationship between the CDKAL1 rs7754840 G/C gene polymorphism and T2DM was observed under a ...[more]

PMID: 26770330

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Project description:BackgroundDiabetes 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.AimWe aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations.MethodsWe 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 ≥ 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).ResultsFourteen 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 (OR = 0.75, 95%CI = 0.64-0.88, p = 0.0003). But the allelic effect model (OR = 0.87, 95%CI = 0.75-1.02, p = 0.08) and the recessive genetic model (OR = 0.85, 95%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 (OR = 0.83, 95%CI = 0.77-0.88, p < 0.00001), the dominant model (OR = 0.79, 95%CI = 0.72-0.87, p < 0.00001), and the recessive model (OR = 0.78, 95%CI = 0.70-0.87, p < 0.0001).ConclusionIn this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations.

Project description:IntroductionCurrent study aimed to find the association of genes polymorphism of CDKAL1, HHEX, CDKN2A/2B, and IGF2BP2 with type 2 diabetes (T2DM) in the population of Uttarakhand.Research design and methodsOverall 469 persons comprising 369 recently diagnosed T2DM cases and 100 healthy control were enrolled in the present study. The polymorphisms were analyzed through the PCR-RFLP technique.ResultsFor the rs10440833 variant (CDKAL1), CC genotype's frequency was significantly high among T2DM subjects than controls and increase the T2DM risk (OR: 4.46, 95% CI: 2.22-8.99, p <0.0001). The c allele was significantly found to increase the T2DM risk (OR: 2.20, 95% CI: 1.54-3.14, p <0.001). In the rs1111875 variant (HHEX), the difference of genotype frequencies among T2DM cases and control was statistically non-significant (p-0.138). We did not observe significant differences in allelic frequencies among T2DM cases and control (p-0.444). In the case of rs10811661 variant (CDKN2A/2B), frequency of both TC (OR: 3.16, 95% CI: 1.84-5.42, p <0.0001) and TT (OR: 5.84, 95% CI: 1.75-19.45, p -0.004) genotype were significantly higher in T2DM cases in comparison with control and significantly associated with higher T2DM risk. Compared to the C allele, a significant increase in T2DM risk was documented with the T allele (OR: 2.47, 95% CI: 1.55-3.92, p <0.001). For rs4402960 variant (IGF2BP2), TT genotype contributed to increased T2DM risk (OR: 4.25, 95% CI: 2.02-8.93, p -0.0001). T allele's frequency was significantly high in T2DM cases in comparison with healthy control. Except WHR, HDL-C, exercise, household chores, standing work more than 3 hours, and family history, significant differences were found between T2DM cases and healthy individuals in all other parameters.ConclusionOur study concluded a significant association of CDKAL1, CDKN2A/2B, and IGF2BP2 polymorphism with T2DM in the Uttarakhand population. For HHEX, the genotype and allelic frequencies difference between T2DM cases and control were statistically non-significant. However, a significant association of HHEX gene polymorphism with T2DM was observed only under the dominant model.

Project description:Background:Type 2 diabetes mellitus (T2DM) is a metabolic disorder with growing prevalence and increasing economic burden. Based on the role of genetics and epigenetic factors on T2DM, we aimed to carry a systematic review and meta-analysis for all miRNA gene polymorphisms and risk of T2DM. Materials and Methods:A computerized literature search was carried out on PubMed, Web of Science, Scopus, Embase, as well as references of relevant review/meta-analysis. Key search terms were "Diabetes Mellitus, Type 2," "MicroRNAs," and "Polymorphism, Single Nucleotide." All types of observational studies from January 1, 1992, to November 30, 2019, were included, without language restriction. Data analysis was performed using R programming language (3.5.2). Level of heterogeneity was obtained by Cochran's Q test (P < 0.05), and subgroup analysis was performed based on ethnicity. Results:Thirty-two polymorphisms from fifteen articles were included. Meta-analysis was carried out based on minor allele frequencies. Seven studies with 2193 cases and 3963 controls were included for rs2910164 polymorphism. In subgroup analysis, there were significant results in Caucasian population in dominant model (odds ratio [OR] =1.12; 95% confidence interval [CI]: 0.83-1.51), homozygote model (OR = 1.78; 95% CI: 1.06-3.00), heterozygote model (OR = 1.77; 95% CI: 1.03-3.05), and recessive model (OR = 1.78; 95% CI: 1.07-2.96). Four studies with 2085 cases and 1933 controls were included for rs895819 polymorphism. Overall, there was no significant result for association with rs895819, but subgroup analysis revealed that minor allele significantly decreased the risk of T2DM in Caucasians by recessive model (OR = 0.34; 95% CI: 0.18-0.66), dominant model (OR = 0.70; 95% CI: 0.52-0.94), homozygote model (OR = 0.32; 95% CI: 0.16-0.62), heterozygote model (OR = 0.37; 95% CI: 0.19-0.74), allelic model (OR = 0.67; 95% CI: 0.52-0.85). Conclusion:The minor allele of rs2910164 may increase the risk of T2DM by leading to lower level of miR-146a. In contrast, minor allele of rs895819 may decrease the risk of T2DM by leading to higher level of miR-27a.

Dataset Information

Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: a meta-analysis of 70141 subjects.

Publications

Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: a meta-analysis of 70141 subjects.

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