Association of the CDKAL1 polymorphism rs10946398 with type 2 diabetes mellitus in adults: A meta-analysis.
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SUBMITTER: Liu X
PROVIDER: S-EPMC7387030 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Association of the CDKAL1 polymorphism rs10946398 with type 2 diabetes mellitus in adults: A meta-analysis.
Liu Xuekui X Liang Jun J Geng Houfa H Xu Wei W Teng Fei F Yang Manqing M
Medicine 20200701 30
Previous studies had reported that the CDKAL1 (cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1) rs10946398 C/A polymorphism associated with type 2 diabetes mellitus (T2DM) in various ethnic groups, however, inconsistent results have been obtained in studies of different populations.We performed a meta-analysis of 13 studies for rs10946398 of CDKAL1 on genetic susceptibility for T2DM.The results showed that CDKAL1 rs10946398 C/A polymorphism associated with T2DM un ...[more]
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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.
| S-EPMC8719992 | biostudies-literature
Project description:The Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene rs7756992 A/G polymorphism has been suggested to be associated with type 2 diabetes mellitus (T2DM), but the individual studies results are still controversial. To explore the association of CDKAL1 gene rs7756992 A/G polymorphism with T2DM, a meta-analysis involving 62,567 subjects from 21 separate studies was conducted. In the whole population, a significant association was found between CDKAL1 gene rs7756992 A/G polymorphism and T2DM under allelic (OR: 1.180, 95% CI: 1.130-1.230, P = 1.60 × 10⁻¹⁴), recessive (OR: 1.510, 95% CI: 1.380-1.660, P = 8.41 × 10⁻¹⁸), dominant (OR: 1.175, 95% CI: 1.109-1.246, P = 6.30 × 10⁻⁸), homozygous (OR: 1.400, 95% CI: 1.282-1.530, P = 8.02 × 10⁻¹⁴), and heterozygous genetic models (OR: 1.101, 95% CI: 1.040-1.166, P = 0.001). CDKAL1 gene rs7756992 A/G polymorphism was significantly associated with T2DM. The person with G allele of CDKAL1 gene rs7756992 A/G polymorphism might be predisposed to T2DM.
| S-EPMC3816287 | biostudies-literature
Project description:BACKGROUND:Large scale association studies have found a significant association between type 2 diabetes mellitus (T2DM) and transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146. However, the quality of data varies greatly, as the studies report inconsistent results in different populations. Hence, we perform this meta-analysis to give a more convincing result. METHODS:The articles, published from January 1st, 2000 to April 1st, 2017, were identified by searching in PubMed and Google Scholar. A total of 56628 participants (34232 cases and 22396 controls) were included in the meta-analysis. A total of 28 studies were divided into 4 subgroups: Caucasian (10 studies), East Asian (5 studies), South Asian (5 studies) and Others (8 studies). All the data analyses were analyzed by the R package meta. RESULTS:The significant association was observed by using the dominant model (OR?=?1.41, CI?=?1.36?-?1.47, p?<?0.0001), recessive model (OR?=?1.58, CI?=?1.48?-?1.69, p?<?0.0001), additive model(CT vs CC) (OR?=?1.34, CI?=?1.28-1.39, p?<?0.0001), additive model(TT vs CC) (OR?=?1.81, CI?=?1.69-1.94, p?<?0.0001)and allele model (OR?=?1.35, CI?=?1.31-1.39, p?<?0.0001). CONCLUSION:The meta-analysis suggested that rs7903146 was significantly associated with T2DM in Caucasian, East Asian, South Asian and other ethnicities.
| S-EPMC5842570 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) accounts for the majority of diabetes cases and affects a significant proportion of the adult population worldwide. Calpain-10 has been implicated in the development of type 2 diabetes, and some polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. Several molecular epidemiological studies were conducted in recent years to evaluate the association between the CAPN10 rs2975760 polymorphism and T2DM risk in diverse populations. However, the results remain conflicting rather than conclusive. We performed a meta-analysis of 8 case-control studies that included 2758 T2DM cases and 2762 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confi dence intervals (CIs). Overall, this meta-analysis showed that the CAPN10 rs2975760 polymorphism was not associated with a significantly type 2 diabetes risk in three genetic models. However, after excluding two study for its heterogeneity, a significantly increased risk was found in all comparisons (for C vs T: OR=1.14, 95% CI=1.03-1.27, I (2)=0, P heterpgeneity=0.420, P b=0.012; for TC vs TT: OR=1.15, 95% CI=1.01-1.30, I (2)=3.8%, P heterpgeneity=0.392, P b=0.030; for CC+TC vs TT: OR=1.16, 95% CI=1.03-1.31, I (2)=3.7%, P heterpgeneity=0.393, P b=0.015). No publication bias was found in the present study. This meta-analysis suggests that the C allele of the CAPN10 rs2975760 polymorphism is associated with an increased T2DM risk. Further large and well-designed studies are needed to confi rm this association.
| S-EPMC4238540 | biostudies-literature
Project description:Background: CDK5 regulatory subunit associated protein 1 like 1 (CDKAL1) is a major pathogenesis-related protein for type 2 diabetes mellitus (T2DM). Recently, some studies have investigated the association of CDKAL1 susceptibility variants, including rs4712523, rs4712524, and rs9460546 with T2DM. However, the results were inconsistent. This study aimed to evaluate the association of CDKAL1 variants and T2DM patients. Methods: A comprehensive meta-analysis was performed to assess the association between CDKAL1 SNPs and T2DM among dominant, recessive, additive, and allele models. Results: We investigated these three CDKAL1 variants to identify T2DM risk. Our findings were as follows: rs4712523 was associated with an increased risk of T2DM for the allele model (G vs A: OR = 1.172; 95% CI: 1.103-1.244; p < 0.001) and dominant model (GG + AG vs AA: OR = 1.464; 95% CI: 1.073-1.996; p = 0.016); rs4712524 was significantly associated with an increased risk of T2DM for the allele model (G vs A: OR = 1.146; 95% CI: 1.056-1.245; p = 0.001), additive model (GG vs AA: OR = 1.455; 95% CI: 1.265-1.673; p < 0.001) recessive model (GG vs AA + AG: OR = 1.343; 95% CI: 1.187-1.518; p < 0.001) and dominant model (GG + AG vs AA: OR = 1.221; 95% CI: 1.155-1.292; p < 0.001); and rs9460546 was associated with an increased risk of T2DM for the allele model (G vs T: OR = 1.215; 95% CI: 1.167-1.264; p = 0.023). The same results were found in the East Asian subgroup for the allele model. Conclusions: Our findings suggest that CDKAL1 polymorphisms (rs4712523, rs4712524, and rs9460546) are significantly associated with T2DM.
| S-EPMC8766415 | biostudies-literature
Project description:IntroductionTo identify the association of the cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene polymorphism with gestational diabetes mellitus (GDM) in the Chinese population.Research design and methodsThis case-control study enrolled 835 pregnant women with GDM and 870 pregnant women without diabetes who underwent antenatal examination during 24 to 28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Trained nurses collected their clinical information and blood samples. CDKAL1 gene rs10440833, rs10946398, rs4712523, rs4712524, rs7754840, rs7756992 and rs9465871 loci were genotyped by Agena MassARRAY system. SPSS V.26.0 software and online SHesis were used to analyze the relationship between CDKAL1 gene polymorphism and GDM susceptibility.ResultsAfter being adjusted for maternal age, prepregnancy body mass index (BMI), parity and family history of type 2 diabetes mellitus (T2DM), CDKAL1 gene rs10440833 (AA vs TT, OR=1.631, 95% CI 1.192 to 2.232), rs10946398 (CC vs AA, OR=1.400, 95% CI 1.028 to 1.905), rs4712523 (GG vs AA, OR=1.409, 95% CI 1.038 to 1.913), rs4712524 (GG vs AA, OR=1.418, 95% CI 1.043 to 1.929) and rs7754840 (CC vs GG, OR=1.407, 95% CI 1.036 to 1.911) polymorphisms were all associated with the increased risk of GDM. In addition, there was a powerful linkage disequilibrium (LD) among rs10946398, rs4712523, rs4712524 and rs7754840 (D'>0.900, r2>0.900). And there were significant differences in haplotype CGGC (OR=1.207, 95% CI 1.050 to 1.387) and AAAG (OR=0.829, 95% CI 0.721 o 0.952, p=0.008) between the GDM group and the control group.Conclusionsrs10440833, rs10946398, rs4712523, rs4712524 and rs7754840 of CDKAL1 gene are associated with GDM susceptibility in central Chinese population.
| S-EPMC10106001 | biostudies-literature
Project description:Background: The Leu72Met polymorphism of ghrelin gene has been associated with genetic predisposition to type 2 diabetes mellitus (T2DM), while conclusions remain conflicting. Hence, we performed this updated meta-analysis to clarify the association between Leu72Met polymorphism and T2DM susceptibility. Methods: Six electronic databases were consulted for articles published before 1 January, 2018. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated under five genetic models to assess this association. We used I 2-test and Q statistics to measure heterogeneity across the included studies. Subgroup analyses and publication bias were also performed. Results: Thirteen case-control studies involving 4720 T2DM patients and 4206 controls were included in this meta-analysis. The overall results using fixed-effects models showed that Leu72Met polymorphism was significantly associated with an increased risk of T2DM under homozygous model (OR = 1.307, 95%CI 1.001-1.705, p = 0.049). Further subgroup analyses stratified by ethnicity revealed that the risk for T2DM was only increased in Asians (homozygous model: OR = 1.335, 95%CI 1.014-1.758, p = 0.040), while decreased in Caucasians (dominant model: OR = 0.788, 95%CI 0.635-0.978, p = 0.030; heterozygous model: OR = 0.779, 95%CI 0.626-0.969, p = 0.025; allelic model: OR = 0.811, 95%CI 0.661-0.995, p = 0.045). Funnel plots were basically symmetrical, and all p-values of Egger's test under five genetic models were >0.050, which indicated no evidence of publication bias. Conclusions: Our results demonstrate that the Leu72Met polymorphism of ghrelin gene may be protective against T2DM in Caucasians, while predisposing to T2DM in Asians.
| S-EPMC6246653 | biostudies-literature
Project description:Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk. Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models). Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082-1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095-5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055-2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148-3.257, p = 0.013) with random effects model. After omitting Gouda's study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004-1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model. Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.
| S-EPMC8646032 | biostudies-literature
Project description:Background and objectivesMany investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis.MethodsAll publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0.ResultsThere were 18 studies identified. The odds ratios (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95-1.12), 1.03 (0.94-1.13) and 1.03 (0.78-1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study.ConclusionIn summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.
| S-EPMC3072982 | biostudies-literature
Project description:BackgroundGenome-wide association study (GWAS) provides an unprecedented opportunity to reveal substantial genetic contribution to type 2 diabetes mellitus (T2DM) and glycemic identification of allelic heterogeneity and population-specific genetic variants, yet it also faces difficulty due to the vast amount of potential confounding factors and limited availability of clinical data. To identify responsible susceptibility loci and genomic polymorphism for T2DM and glycemic traits, we have systematically investigated a genome-wide association study related to T2DM. Although GWAS has captured many common genetic variations, which are related to T2DM, each risk allele (RA) of single-nucleotide polymorphisms (SNPs) at these loci is not conclusive. Therefore, it is common to present a combination of several SNPs to infer T2DM risk, yet it is still insufficient to be deterministic. To streamline the identification of a deterministic genetic variation in T2DM, we developed this meta-analysis as a showcase to comprehensively identify the association between cumulative RAs and T2DM risk by combining different studies in reported literature and databases. After all, we identified that PGC-1α rs8192678 polymorphism can be considered as a potentially deterministic biomarker in T2DM risk. Previous studies have potentially linked PGC-1α rs8192678 polymorphism to type 2 diabetes mellitus (T2DM) risk, but the results remain inconsistent in different populations and are not conclusive. We developed a new meta-analysis approach to systematically identify the association between PGC-1α rs8192678 polymorphism and T2DM, and we have comprehensively assessed different ethnic groups to validate our findings.MethodsWe performed comprehensive information retrieval and knowledge discovery meta-analysis by searching extensively published literature and different electronic databases to acquire eligible studies for the above association study. We developed a method to use pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) in five genetic models (allelic, dominant, recessive, homozygous, and heterozygous genetic models) to identify the relationship among ethnicity subgroup analyses comprehensively.ResultsWe identified 20 eligible studies consisting of 16,182 subjects (8,038 cases and 8,144 controls) in our meta-analysis. PGC-1α rs8192678 polymorphisms of all subjects showed a significant association with T2DM susceptibility under all genetic models: allelic (OR: 1.24, 95% CI: 1.13-1.35), dominant (OR: 1.27, 95% CI: 1.14-1.42), recessive (OR: 1.24, 95% CI: 1.14-1.36), homozygous (OR: 1.40, 95% CI: 1.20-1.64), and heterozygous (OR: 1.20, 95% CI: 1.06-1.35). In the subgroup analysis, we identified a significant association between PGC-1α rs8192678 polymorphism and T2DM in the Caucasian and Indian populations under all genetic models we investigated. This is the most comprehensive study of the subject to date.ConclusionOur development of meta-analysis revealed that the minor allele (A) carriers, especially AA genotype carriers, can lead to risk of T2DM in the Caucasian and Indian populations. This is the first report that such risk has been confirmed. Our finding shed new light into the genetic alteration in T2DM.
| S-EPMC6421808 | biostudies-literature