scholarly journals A Novel Polymorphism (rs35612982) in CDKAL1 Is a Risk Factor of Type 2 Diabetes: A Case-Control Study

2019 ◽  
Vol 44 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Yanni Tian ◽  
Jing Xu ◽  
Ting Huang ◽  
Jiaqi Cui ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Case Control Study ◽  
Insulin Level ◽  
Northwest China ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
The Status ◽  
Control Study

Background: The interaction of environmental factors and genetic factors may contribute to the risk of type 2 diabetes (T2D). We aimed to investigate whether age, gender, body mass index (BMI) and lifestyle factors have an effect on the association between the CDKAL1 polymorphisms and T2D. Methods: Eight single nucleotide polymorphisms in CDKAL1 were genotyped by Agena MassARRAY in 508 T2D patients and 503 controls. The association between the CDKAL1 polymorphisms and T2D was evaluated using logistic regression model by calculating OR and 95% CIs. Results: We found a significant association between CDKAL1 polymorphisms (rs4712523, OR 1.42, p = 9.44 × 10–5; rs4712524, OR 1.38, p = 3.28 × 10–4; rs10946398, OR 1.43, p = 6.21 × 10–5; rs7754840, OR 1.43, p = 6.33 × 10–5; rs35612982, OR 1.34, p = 0.0010; and rs10440833, OR 1.32, p = 0.0018) and T2D risk among the Han population from Northwest China. We also found that genetic variants of CDKAL1 could modify the risk of T2D that might be influenced by age, BMI and the status of smoking and drinking. Besides, rs35612982-CT (p = 0.038) and rs10440833-AT (p = 0.044) genotypes were higher insulin level. Conclusion: CDKAL1 rs35612982 (C/T) polymorphism, as a new polymorphism, was associated with the increased risk of T2D in the Han Chinese population. Moreover, the contribution of CDKAL1 polymorphisms to T2D risk seems to be associated with age, gender, BMI, smoking and drinking.

scholarly journals Association of genetic polymorphisms of SelS with Type 2 diabetes in a Chinese population

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Long Zhao ◽  
Ying-Ying Zheng ◽  
You Chen ◽  
Yi-Tong Ma ◽  
Yi-Ning Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Polymorphisms ◽  
Chinese Population ◽  
Case Control Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
The Difference ◽  
The Relationship ◽  
Control Study

Background: Selenoprotein S (SelS) gene expression is positively correlated to triglyceride (TG) concentrations and is associated with diabetes in animal model. However, the relationship between genetic polymorphisms of SelS and Type 2 diabetes (T2DM) remains unclear. Methods: In the present study, we genotyped four single nucleotide polymorphisms (rs12910524, rs1384565, rs2101171, rs4965814) of SelS gene using TaqMan genotyping method in a case–control study (1947 T2DM patients and 1639 control subjects). Results: We found both rs1384565 CC genotype (12.1 compared with 6.6%, P<0.001) and C allele (35.2 compared with 24.4%, P<0.001) were more frequent in the T2DM patients than in the controls. Logistic regression analysis suggested after adjustment of other confounders, the difference remained significant between the two groups (CC compared with TT, P=0.002, OR = 1.884, 95% CI: 1.263–2.811; CT compared with TT, P<0.001, OR = 1.764, 95% CI: 1.412–2.204). Conclusion: The present study suggested that genetic polymorphisms of SelS were associated with T2DM in a Chinese population.

scholarly journals Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case–control study and meta-analysis

2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia
Keyword(s):  
Type 2 Diabetes ◽  
Case Control Study ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Case Control ◽  
Increased Risk ◽  
Key Enzyme ◽  
Control Study

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.

scholarly journals In vivo reporter assays uncover changes in enhancer activity caused by type 2 diabetes associated SNPs

2020 ◽  
Author(s):  
Ada Admin ◽  
Ana Eufrásio ◽  
Chiara Perrod ◽  
Marta Duque ◽  
Fábio J.Ferreira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Nucleotide Mutation ◽  
Reporter Assays ◽  
Coding Snp

Many single nucleotide polymorphisms (SNPs) associated to type 2 diabetes overlap with putative endocrine pancreatic enhancers, suggesting that these SNPs modulate enhancer activity and consequently, gene expression. We performed <i>in vivo</i> mosaic transgenesis assays in zebrafish to quantitatively test the enhancer activity of type 2 diabetes-associated <i>loci</i>. Six out of ten tested sequences are endocrine pancreatic enhancers. The risk variant of two sequences decreased enhancer activity, while in another two incremented it. One of the latter (rs13266634) locates in a <i>SLC30A8 </i>exon, encoding a tryptophan-to-arginine substitution that decreases <i>SLC30A8 </i>function, being the canonical explanation for type 2 diabetes risk association. However, other type 2 diabetes associated SNPs that truncate SLC30A8, confer protection to this disease, contradicting this explanation. Here, we clarify this incongruence showing that rs13266634 boosts the activity of an overlapping enhancer, suggesting a SLC30A8 gain-of-function as the cause for the increased risk for the disease. We further dissected the functionality of this enhancer finding a single nucleotide mutation sufficient to impair its activity. Overall, this work assesses <i>in vivo</i> the importance of disease-associated SNPs in the activity of endocrine pancreatic enhancers, including a poorly explored case where a coding SNP modulates the activity of an enhancer.

scholarly journals Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yijun Wang ◽  
Gang Chen ◽  
Qingyun Tu ◽  
Junxia Wu ◽  
Yu Qin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Diseases ◽  
Proteinase K ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Polymerase Chain ◽  
And Gender

Objectives. AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods. Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol–chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results. The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions. AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

scholarly journals Relationship between the IL23R SNPs and Crohn’s Disease Susceptibility and Phenotype in the Polish and Bosnian Populations: A Case-Control Study

2019 ◽  
Vol 16 (9) ◽  
pp. 1551
Author(s):  
Krzysztof Borecki ◽  
Iwona Zawada ◽  
Nermin Nusret Salkić ◽  
Beata Karakiewicz ◽  
Grażyna Adler
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Case Control Study ◽  
Age Of Onset ◽  
Severe Disease ◽  
Polish Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Control Study

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn’s disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.

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