What have we learnt from genetic studies of type 2 diabetes in Chinese?
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ABSTRACT:
SUBMITTER: Jia W
PROVIDER: S-EPMC4019297 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
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What have we learnt from genetic studies of type 2 diabetes in Chinese?
Journal of diabetes investigation 20111001 5
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Project description:Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants. Pathogenicity was defined according to the standards and guidelines of the American College of Medical Genetics and Genomics. We identified 33 rare variants predicted to be deleterious in 39 patients. The fasting [1.57(1.06-2.22) ng/ml] and postprandial C-peptide levels [2.8(1.75-4.46) ng/ml] of the patients with such WFS1 variations were lower than those of the patients without WFS1 variation [2.09(1.43-3.05) and 4.29(2.76-6.07) respectively, ng/ml]. Six (0.9%) patients carried pathogenic or likely pathogenic variants; they met the diagnostic criteria for WFS1-DM according to the latest guidelines, but typical phenotypes of Wolfram syndrome were seldom observed. They were diagnosed at an earlier age and usually presented with an absence of obesity, impaired beta cell function, and the need for insulin treatment. WFS1-DM is usually mistakenly diagnosed as type 2 diabetes, and genetic testing is helpful for individualized treatment.
| S-EPMC10241780 | biostudies-literature
Project description:Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (ABCA1, GCKR, BAZ1B, TOMM40, DOCK7, HNF1A, and HNF4A) were genotyped. After adjusting for multiple covariates, SNPs in ABCA1, GCKR, BAZ1B, TOMM40, and HNF1A were identified as significantly associated with triglyceride levels in T2D patients (P < 0.05). The associations between the SNPs in ABCA1 (rs3890182), GCKR (rs780094), and BAZ1B (rs2240466) remained significant even after correction for multiple testing (P = 8.85×10(-3), 7.88×10(-7), and 2.03×10(-6), respectively). BAZ1B (rs2240466) also was associated with the total cholesterol level (P = 4.75×10(-2)). In addition, SNP rs157580 in TOMM40 was associated with the low-density lipoprotein cholesterol level (P = 6.94×10(-3)). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.
| S-EPMC4529182 | biostudies-literature
Project description:BackgroundSeveral studies have reported the association of PTPN2 gene with type 1 diabetes mellitus (T1DM) in many populations but not in the Chinese Han population. Therefore, the goal of our study was to replicate the reported association between 2 single-nucleotide polymorphisms (SNPs; rs478582 and rs2542151) in the PTPN2 gene and T1DM in Chinese Han children.Material and methodsThis case-control study included 141 Chinese Han children with T1DM and 282 healthy controls. Genetic variants of rs478582 and rs2542151 in PTPN2 gene were performed by PCR amplification followed by restriction fragment length polymorphism method.ResultsNo difference was observed in association of rs478582 in The PTPN2 gene and T1DM. The distribution of allele frequency of rs2542151 differed significantly between T1DM patients and healthy controls (OR, 0.6; 95%CI: 0.44 to 0.95; and P=0.024). Dominant model of rs254215 also was associated with T1DM (OR, 0.6; 95%CI: 0.40 to 0.96; and P=0.032). Younger age at onset in G carriers appeared to increase the risk for T1DM (P=0.030).ConclusionsThe findings suggested that rs2542151 SNP in The PTPN2 gene was associated with T1DM in Chinese Han children. Further studies with larger sample sizes involving gene-gene interactions are urgently needed.
| S-EPMC4566944 | biostudies-literature
Project description:OBJECTIVES:The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes. BACKGROUND:No study has examined the effects of these genetic variants on CHD in diabetic patients. METHODS:We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects). RESULTS:Five single-nucleotide polymorphisms, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001). Individuals with GRS ?8 (19% of diabetic subjects) had almost a 2-fold increase in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with individuals with GRS ?5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p < 0.001) when the GRS was added to a model including clinical predictors in the combined samples. CONCLUSIONS:Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.
| S-EPMC3240896 | biostudies-literature
Project description:Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.
| S-EPMC3580778 | biostudies-literature
Project description:ObjectiveTo evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC).MethodsIncluded in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models.ResultsDuring a median follow-up of 8.08 years (range, 0.01-16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05-1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28-3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04-20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups.ConclusionsOur study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism.
| S-EPMC4332504 | biostudies-literature
Project description: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.
| S-EPMC6259018 | biostudies-literature
Project description:ObjectiveThe aim of this study was to determine whether TPCN2 genetic variants are associated with type 2 diabetes and to elucidate which variants in TPCN2 confer diabetes susceptibility in the Chinese population.Research design and methodsThe sample population included 384 patients with type 2 diabetes and 1468 controls. Anthropometric parameters, glycemic and lipid profiles and insulin resistance were measured. We selected 6 TPCN2 tag single nucleotide polymorphisms (rs35264875, rs267603153, rs267603154, rs3829241, rs1551305, and rs3750965). Genotypes were determined using a Sequenom MassARRAY SNP genotyping system.ResultsUltimately, we genotyped 3 single nucleotide polymorphisms (rs3750965, rs3829241, and rs1551305) in all individuals. There was a 5.1% higher prevalence of the rs1551305 variant allele in type 2 diabetes individuals (A) compared with wild-type homozygous individuals (G). The AA genotype of rs1551305 was associated with a higher diabetes risk (p<0.05). The distributions of rs3829241 and rs3750965 polymorphisms were not significantly different between the two groups. HOMA-%B of subjects harboring the AA genotype of rs1551305 decreased by 14.87% relative to the GG genotype.ConclusionsTPCN2 plays a role in metabolic regulation, and the rs1551305 single nucleotide polymorphism is associated with type 2 diabetes risk. Future work will begin to unravel the underlying mechanisms.
| S-EPMC4769022 | biostudies-literature
Project description:PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China. We designed a case-control study including 662 patients diagnosed with T2DM and 1220 control subjects. Four single-nucleotide polymorphisms (rs11583680, rs2483205, rs2495477 and rs562556) of PCSK9 gene were genotyped using the improved multiplex ligation detection reaction technique. For rs2483205, the distribution of genotypes, dominant model (CC vs CT + TT), overdominant model (CC + TT vs CT) showed significant differences between T2DM patients and the controls (P = 0.011 and P = 0.041 respectively). For rs2495477, the distribution of genotypes, the dominant model (AA vs GA + GG) showed significant differences between T2DM patients and the controls (P = 0.024). Logistic regression analysis suggested after adjustment of other confounders, the differences remained significant between the two groups [for rs2483205 CC vs CT + TT: odds ratio (OR) = 1.321, 95% confidence interval (CI) 1.078-1.617, P = 0.007; CC + TT vs CT: OR = 1.255, 95% CI 1.021-1.542, P = 0.03; for rs2495477 AA vs GA + GG: OR = 1.297, 95% CI 1.060-1.588, P = 0.012]. The present study indicated that CT + TT genotype and CT genotype of rs2483205, as well as GA + GG genotype of rs2495477 in PCSK9 gene were associated with an increased risk of type 2 diabetes in the Uygur population in Xinjiang.
| S-EPMC9219175 | biostudies-literature
Project description:Background/Objectives: Genes and environments were transmitted across generations. Parents' genetics influence the environments of their offspring; these two modes of inheritance can produce a genetic nurture effect, also known as indirect genetic effects. Such indirect effects may partly account for estimated genetic variance in T2D. However, the well-established specific genetic risk factors about genetic nurture effect for T2D are not fully understood. This study aimed to investigate the genetic nurture effect on type 2 diabetes and reveal the potential underlying mechanism using publicly available data. Methods: Whole-genome genotyping data of 881 offspring and/or their parents were collected. We assessed SNP-level, gene-based, and pathway-based associations for different types of genetic effects. Results: Rs3805116 (β: 0.54, p = 4.39 × 10-8) was significant for paternal genetic nurture effects. MRPS33 (p = 1.58 × 10-6), PIH1D2 (p = 6.76 × 10-7), and SD1HD (p = 2.67 × 10-6) revealed significantly positive paternal genetic nurture effects. Five ontologies were identified as enrichment in both direct and indirect genetic effects, including flavonoid metabolic process and antigen processing and presentation via the MHC class Ib pathway. Two pathways were only enriched in paternal genetic nurture effects, including the transforming growth factor beta pathway. Tissue enrichment of type 2 diabetes-associated genes on different genetic effect types was performed using publicly available gene expression data from the Human Protein Atlas database. We observed significant gene enrichment in paternal genetic nurture effects in the gallbladder, smooth muscle, and adrenal gland tissues. Conclusions: MRPS33, PIH1D2, and SD1HD are associated with increased T2D risk through the environment influenced by paternal genotype, suggesting a novel perspective on paternal contributions to the T2D predisposition.
| S-EPMC11761613 | biostudies-literature