Association study of genetic variants of 17 diabetes‐related genes/loci and cardiovascular risk and diabetic nephropathy in the <scp>C</scp>hinese <scp>S</scp>he population (中国畲族人群17个糖尿病相关基因位点的遗传变异与心血管风险和糖尿病肾病的相关性)

Chen, Gang; Xu, Yuan; Lin, Yuan; Lai, Xin; Yao, Jin; Huang, Baoying; Chen, Zichun; Huang, Huibin; Fu, Xianguo; Li, Lin; Lai, Shenghan; Wen, Junping

doi:10.1111/1753-0407.12025

Cited by 52 publications

(40 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eligible criteria included (1) candidate-gene association studies for T2DM published in peer-reviewed journal, (2) participants recruited from independent populations, (3) genotype information sufficient to calculate allele counts, (4) candidate genes tested in our study and (4) study population restricted to Han Chinese. A total of 21 studies that fulfill were indentified [13], [16]–[35]. Full-text manuscripts were obtained for all studies.…”

Section: Methodsmentioning

confidence: 99%

“…Full-text manuscripts were obtained for all studies. One study was excluded because its study population was confined to She Chinese population[35]. Data extraction was performed and examined independently by two reviewers (YCC and YHY).All procedures were conformed to the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) guidelines for meta-analysis[36].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

Chang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

BackgroundSeveral genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated.MethodsWe analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese.ResultsFive risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations.ConclusionWe confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

Chang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Recent studies have further shown the effects of the FTO gene on the risk of BMI-related outcomes such as diabetes [33], neural tube defects [33] and Alzheimer's disease [34]. Although the effects of obesity on the development of metabolic and cardiovascular problems are well studied, much less is known about its impact on the infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Obesity-associated gene FTO rs9939609 polymorphism in relation to the risk of tuberculosis

Yan

Wang

Pan³

et al. 2014

BMC Infect Dis

View full text Add to dashboard Cite

BackgroundObesity is known to affect cell-mediated immune responses. Recent studies have revealed that genetic polymorphisms in the fat mass and obesity associated (FTO) gene are related to human obesity. We hypothesize that this gene may also play a role in the risk of immune-related infectious diseases such as tuberculosis.MethodsThis case-control study included 1625 pulmonary tuberculosis cases and 1570 unaffected controls recruited from the Jiangsu province in China. Single nucleotide polymorphisms (SNPs), rs9939609 and rs8050136, in the FTO gene were genotyped using TaqMan allelic discrimination assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the unconditional logistic regression model.ResultsWe observed a significant association between the genetic polymorphism rs9939609 and tuberculosis risk. Compared with the common genotype TT, individuals carrying AA had a significantly increased risk, with an OR of 3.77 (95% CI: 2.26-6.28). After adjusting for potential confounders, the relationship remains significant. An additive model showed that carriers of an allele A had a 26% increased risk of tuberculosis compared with the T allele (OR: 1.26, 95% CI: 1.08-1.48). Compared with the common haplotype rs9939609T-rs8050136C, the haplotype rs9939609A-rs8050136C was related to an increased risk of tuberculosis (OR = 6.09, 95% CI: 3.27-12.34).ConclusionsThe FTO polymorphism rs9939609 is associated with a risk of pulmonary tuberculosis in the Chinese population.

show abstract

“…In addition, the expression of ZnT8 has been demonstrated to be decreased in the β cells of diabetic mice (19). A ZnT8 (or SLC30A8) gene polymorphism has been identified, and is associated with type 2 diabetes (20)(21)(22). Furthermore, an autoantibody to ZnT8 is widely considered as a biomarker of autoimmune diabetes (23,24).…”

mentioning

confidence: 99%

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

Cheng¹,

Zhang²,

Chen³

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Zinc transporter 8 (ZnT8) is exclusively expressed in the pancreatic islet and is essential for insulin crystallization, hexamerization and secretion. Tumor necrosis factor α-induced protein-3 (TNFAIP3) is a zinc finger protein that serves a major role in the negative feedback regulation of NF-κB signaling in response to multiple stimuli, and is a central regulator of immunopathology. Although the role of TNFAIP3 in diabetes has been extensively studied, its effect on ZnT8 has not been fully elucidated. The present study aimed to verify whether proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), are able to affect ZnT8 expression in islet cells. In addition, the study aimed to determine the effect of TNFAIP3 overexpression on cytokine-altered ZnT8 activity, considering its effect on NF-κB signaling. Cell-based studies using NIT-1 cells overexpressing TNFAIP3 were used to assess the effect of cytokines on ZnT8 and NF-κB activation, as well as the effect of TNFAIP3 on ZnT8 expression. Western blot analysis and immunofluorescence staining were employed to determine the protein expression and NF-κB activation, respectively. The results indicated that cytokine stimulation led to TNFAIP3 upregulation, ZnT8 downregulation and NF-κB activation. Furthermore, TNFAIP3 overexpression protected ZnT8 from cytokine-induced downregulation. In conclusion, the current results suggest that inflammation or TNFAIP3 dysfunction may be involved in the pathogenesis of diabetes via ZnT8 expression, besides from islet cell apoptosis. In addition, restricting inflammation and enhancing TNFAIP3 expression may exert a positive effect in diabetes prevention, treatment and pancreatic cell transplantation. IntroductionDiabetes, a class of metabolic diseases that are prevalent worldwide affecting 422 million people in 2014 according to the World Health Organization (1), is characterized by hyperglycemia and can cause severe damage to different organs, particularly the eyes, kidneys, nerves, heart and blood vessels. According to the American Diabetes Association, the disease can be classified into two main types, including type 1 and type 2 diabetes (2). Type 1 diabetes results from a cell-mediated autoimmune attack on β cells, whereas type 2 diabetes is a low-grade, chronic inflammatory disease that shares a common final pathway with type 1 diabetes, in which activation of the nuclear factor κB (NF-κB) signaling pathway causes a reduction in pancreatic β cells (3-10).Zinc participates in numerous biological processes, and is essential for the correct processing, storage, secretion, and function of insulin in pancreatic β cells (11-13). Zinc flux is controlled by two types of transporters: The zinc transporter (ZnT; also known as SLC30A) family, and the Zrt-and Irt-like protein (ZIP) family. Typically, the ZnT family regulates Zn 2+ efflux out of the cytoplasm, while the ZIP family regulates Zn 2+ influx into the cytoplasm. Although 10 ZnTs and 14 ZIPs have been identified in mammals, ZnT8 is exclusiv...

show abstract

Association study of genetic variants of 17 diabetes‐related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population (中国畲族人群17个糖尿病相关基因位点的遗传变异与心血管风险和糖尿病肾病的相关性)

Cited by 52 publications

References 39 publications

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

Obesity-associated gene FTO rs9939609 polymorphism in relation to the risk of tuberculosis

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

Contact Info

Product

Resources

About