scholarly journals Evidence for Association of the E23K Variant ofKCNJ11Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Khaled Lasram ◽  
Nizar Ben Halim ◽  
Sana Hsouna ◽  
Rym Kefi ◽  
Imen Arfa ◽  
...  

Aims. Genetic association studies have reported the E23K variant ofKCNJ11gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations.Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.).Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, andP=0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, andP<10-3and OR = 1.33, 95% CI = 1.13–1.56, andP=0.001, resp.).Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant ofKCNJ11and Type 2 diabetes among Tunisians and Arabs.

2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia

ObjectiveThe type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T3) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.Design and methodsA case–control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms ‘rs225014’ odds ratio (OR) ‘thr92ala’ OR ‘T92A’ OR ‘dio2 a/g’.ResultsIn the case–control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03–1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78–2.51)), Grarup (OR 1.09 (95% CI 0.92–1.29)), and Maia (OR 1.22 (95% CI 0.78–1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03–1.36, P=0.02).ConclusionsOur results indicate that in a case–control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T3 concentration in skeletal muscle on DM2 pathogenesis.


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.


2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p &lt; 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044486 ◽  
Author(s):  
Per Svensson ◽  
Robin Hofmann ◽  
Henrike Häbel ◽  
Tomas Jernberg ◽  
Per Nordberg

AimsThe risks associated with diabetes, obesity and hypertension for severe COVID-19 may be confounded and differ by sociodemographic background. We assessed the risks associated with cardiometabolic factors for severe COVID-19 when accounting for socioeconomic factors and in subgroups by age, sex and region of birth.Methods and resultsIn this nationwide case–control study, 1.086 patients admitted to intensive care with COVID-19 requiring mechanical ventilation (cases), and 10.860 population-based controls matched for age, sex and district of residency were included from mandatory national registries. ORs with 95% CIs for associations between severe COVID-19 and exposures with adjustment for confounders were estimated using logistic regression. The median age was 62 years (IQR 52–70), and 3003 (24.9%) were women. Type 2 diabetes (OR, 2.3 (95% CI 1.9 to 2.7)), hypertension (OR, 1.7 (95% CI 1.5 to 2.0)), obesity (OR, 3.1 (95% CI 2.4 to 4.0)) and chronic kidney disease (OR, 2.5 (95% CI 1.7 to 3.7)) were all associated with severe COVID-19. In the younger subgroup (below 57 years), ORs were significantly higher for all cardiometabolic risk factors. The risk associated with type 2 diabetes was higher in women (p=0.001) and in patients with a region of birth outside European Union(EU) (p=0.004).ConclusionDiabetes, obesity and hypertension were all independently associated with severe COVID-19 with stronger associations in the younger population. Type 2 diabetes implied a greater risk among women and in non-EU immigrants. These findings, originating from high-quality Swedish registries, may be important to direct preventive measures such as vaccination to susceptible patient groups.Trial registration numberClinicaltrial.gov (NCT04426084).


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ganesh Chauhan ◽  
Ismeet Kaur ◽  
Rubina Tabassum ◽  
Om Prakash Dwivedi ◽  
Saurabh Ghosh ◽  
...  

Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variantMTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78(95%  CI=0.67–0.92),P=0.003) and was also associated with 2 h postload plasma glucose (P=0.04), high-density lipoprotein cholesterol (P=0.004), and total cholesterol (P=0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.


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