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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ning Xu ◽  
Ting-Ting Zhang ◽  
Wen-Jia Han ◽  
Li-Ping Yin ◽  
Nan-Zheng Ma ◽  
...  

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 ≥ 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 ( 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 ). Conclusion. In this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations.

2016 ◽  
Vol 6 (2) ◽  
pp. 76-86 ◽  
Author(s):  
Jonny Karunia Fajar

Introduction: Several studies regarding the association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus (T2DM) showed inconsistent results. This study aimed to investigate the association of ENPP1 K121Q gene polymorphism with T2DM risk using meta-analysis. The study was limited to the American, European, and African populations.Methods: PubMed and Embase databases were searched for eligible publications. The following information was extracted from each study: name of first author, publication year, country of origin, sample size of cases and controls, and size of each allele. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between ENPP1 K121Q gene polymorphism and T2DM risk were assessed using random or fixed effect model. A comprehensive meta-analysis (CMA) 2.0 was used to analyze the data.Results: Nineteen studies (17717 cases/28022 controls) on the association between ENPP1 K121Q gene polymorphism and T2DM risk were included in this meta-analysis. The results indicated that the ENPP1 K121Q gene polymorphism was associated with increased T2DM risk (Q vs. K genetic model, OR 95% CI = 1.11 [1.02–1.22], p = 0.014; QQ vs. KK + KQ, OR 95% CI = 1.14 [1.01–1.23], p = 0.039) and decreased T2DM risk (K vs. Q, OR 95% CI = 0.90 [0.82–1.00], p = 0.014; KK vs. KQ + QQ, OR 95% CI = 0.89 [0.80–0.98], p = 0.024).Conclusions: The results indicate that the ENPP1 K121Q gene polymorphism is associated with the risk of T2DM in the American, European, and African populations.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen-Jia Han ◽  
Jian-Yi Deng ◽  
Hua Jin ◽  
Li-Ping Yin ◽  
Jin-Xia Yang ◽  
...  

Background. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective. To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods. A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger’s test were used to evaluate the publication bias of the selected included literature. Results. Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001 ), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001 ) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. Conclusion. This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.


2015 ◽  
Vol 62 (2) ◽  
pp. 183-194 ◽  
Author(s):  
Yan-yan Li ◽  
Ge Gong ◽  
Hong-yu Geng ◽  
Zhi-jian Yang ◽  
Chuan-wei Zhou ◽  
...  

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiao-xuan Yu ◽  
Min-qi Liao ◽  
Yu-fei Zeng ◽  
Xu-ping Gao ◽  
Yan-hua Liu ◽  
...  

Background. Previous studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive. Objective. To examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies. Methods. Five electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence. Results. 49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression. Conclusion. This meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Madan ◽  
S Sohal ◽  
B Parapid ◽  
L Sperling ◽  
J L Januzzi ◽  
...  

Abstract Background Randomized studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce major cardiovascular events in patients with type 2 diabetes mellitus. However, it is not known whether there are significant sex-based differences in the cardioprotective role of SGLT-2 inhibitors. Purpose To investigate whether sex differences exist in reduction of major cardiovascular events (MACE)in patients with type 2 diabetes mellitus when treated with SGLT2i. Methods A comprehensive PubMed search was conducted using keywords, (“Diabetes” AND (“Dapagliflozin” OR “Empagliflozin” OR “Canagliflozin” OR “Ertugliflozin”) AND “Outcomes”) that resulted in a total of 221 studies. Studies were included in our meta-analysis if they were randomized controlled trials, placebo-controlled, reported MACE as the primary outcome and reported sex-based subgroup analyses of these outcomes. Only 2 RCTs (EMPA-REG and DECLARE-TIMI 58) met our inclusion criteria.The sex-based event data for both trials was pooled to calculate risk ratios (RR) with 95% confidence intervals (CI). Analyses was performed using Comprehensive Meta-analysis (CMA) software. Fixed effect models, random effect models and mixed effect models were used. Results Pooled datafrom the 2 RCTs (EMPA-REG and DECLARE-TIMI 58) resulted in a total of 24,180 patients who were included in our primary analysis. Of these, 2331 patients were reported to have MACE. In our pooled data, SGLT2i reduced MACE in patients with diabetes with an overall risk ratio of 0.92 (0.85–0.99), p=0.03 (I2=0, p=0.31)using fixed effect model (Table 1). We also performed subgroup analysis of the pooled data categorizing by sex and using mixed effect model. Our subgroup analysis by sex showed a Q statistic of 1.88 with p-value of 0.17 suggesting that there is no significant difference in MACE reduction between men and women with diabetes when treated with SGLT2i. However, on further analyzing the sex differences in the individual trials, we found that women may have greater reduction in MACE compared with their male counterparts (RR in females: 0.66 (0.42–1.04); RR in males: 0.92 (0.84–1.00)), however this finding did not meet statistical significance (Table 2). Conclusion Our meta-analysis included the pooled data from 2 major RCTs (EMPA-REG and DECLARE-TIMI 58) assessing the cardioprotective role of SGLT2i in diabetic patients and shows that SGLT2i significantly reduce the risk of major adverse CV events in patients with type 2 diabetes mellitus. However, we did not find any significant sex-based differences in reduction of MACE between men and women with diabetes when treated with SGLT2i.


PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61153 ◽  
Author(s):  
Yan-yan Li ◽  
Zhi-jian Yang ◽  
Chuan-wei Zhou ◽  
Xiang-ming Wang ◽  
Yun Qian ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Ha Young Yoon ◽  
Min Hye Lee ◽  
Yubin Song ◽  
Jeong Yee ◽  
Gonjin Song ◽  
...  

BackgroundThe ATP-binding cassette transporter A1 (ABCA1) is likely associated with the risk of type 2 diabetes mellitus (T2DM) via β cell function modification, but the evidence on the association remains unclear. This study aimed to investigate the relationship between the ABCA1 69C&gt;T polymorphism and the risk of T2DM through a systematic review and meta-analysis.Materials and MethodsThe PubMed, Web of Science, and Embase databases were searched for qualified studies published until August 2020. Studies that included the association between the ABCA1 69C&gt;T polymorphism and the risk of T2DM were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsWe analyzed data from a total of 10 studies involving 17,742 patients. We found that the CC or CT genotype was associated with increased risk of T2DM than the TT genotype (OR, 1.41; 95% CI, 1.02-1.93). In the Asian population, the C allele carriers had a higher risk of T2DM than those with the TT genotype; the ORs of the CC and CT genotypes were 1.80 (95% CI, 1.21-2.68) and 1.61 (95% CI, and 1.29-2.01), respectively.ConclusionsThis meta-analysis confirmed that the ABCA1 69C&gt;T genotype showed a decrease risk of T2DM compared to the CC or CT genotypes.


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