Showing papers by "Rong Zhang published in 2009"

PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.

Abstract: Background Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism. Methods/Principal Findings Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006). Conclusions/Significance The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.

Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population.

Abstract: Aims/hypothesis Recent genome-wide association studies in East Asian populations reported that single nucleotide polymorphisms (SNPs) in KCNQ1 are associated with type 2 diabetes. The aim of this study was to validate this finding in a Chinese population.

A genetic variant of G6PC2 is associated with type 2 diabetes and fasting plasma glucose level in the Chinese population

Abstract: Single nucleotide polymorphisms (SNPs) in G6PC2 have been reported to be associated with fasting plasma glucose level in several populations of European descent. However, whether G6PC2 variants have a similar effect in other ethnic groups is unknown. The aim of this study was to investigate the effect of common variants of G6PC2 on type 2 diabetes and related clinical features in a Chinese population. We selected four SNPs, rs13387347, rs2232316, rs492594 and rs16856187, tagging all the common variants spanning the G6PC2 gene (r 2 ≥ 0.8) based on HapMap Chinese data, and genotyped them in a group of 3,676 Shanghai Chinese individuals, comprising 1,876 cases and 1,800 controls. Three SNPs were nominally associated with type 2 diabetes, with rs16856187 showing the strongest evidence for association (p = 0.0009, empirical p = 0.0047). Further conditional analysis revealed that the association signal arose from an individual SNP, rs16856187. This SNP was also associated with fasting plasma glucose level in participants with normal glucose regulation (p = 0.0002), with the fasting plasma glucose level observed to increase by 0.067 mmol/l with each copy of the rare C allele. In this study we identified a novel risk-conferring G6PC2 SNP for type 2 diabetes in a Chinese population and confirmed the previous finding that G6PC2 variants are associated with fasting plasma glucose concentration.

Common variants of hepatocyte nuclear factor 1β are associated with type 2 diabetes in a Chinese population.

Abstract: OBJECTIVE Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1 β were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmo Preventive Project produced conflicting results, and the role for HNF1 β in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1 β gene in a Chinese population. RESEARCH DESIGN AND METHODS Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes ( n = 1,859) and normal glucose regulation ( n = 1,785). RESULTS Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05–1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects ( P = 0.0228). CONCLUSIONS The result of this study provides evidence that variants in the HNF1 β region contribute to susceptibility to type 2 diabetes in the Chinese population.

Association of apelin genetic variants with type 2 diabetes and related clinical features in Chinese Hans.

Abstract: BACKGROUND: Apelin is an adipokine that contributes to the pathogenesis of type 2 diabetes. The plasma levels of apelin increased in obese patients and diabetic subjects. This study aimed to investigate the effects of apelin genetic variants on type 2 diabetes and related quantitative traits. METHODS: We selected three single nucleotide polymorphisms (SNPs) that could capture all common variants in APLN gene region and genotyped them in 1892 type 2 diabetic patients and 1808 normal glucose regulation controls. The clinical features related to glucose metabolism were measured in the controls. The comparison of allele and genotype distribution in the cases and controls were performed by using chi(2) tests. The association between SNPs and quantitative traits were analyzed using Wilcoxon's rank-sum test. RESULTS: None of the SNPs or haplotypes showed evidence of association to type 2 diabetes. However, rs2235306 was nominally associated with fasting plasma glucose levels in the male subjects with normal glucose regulation ((4.93 +/- 0.03) vs (5.01 +/- 0.03) mmol/L, P = 0.04). No significant difference was observed between all three SNPs and other variables. CONCLUSIONS: APLN SNP rs2235306 was associated with fasting plasma glucose levels in males. It suggests that APLN genetic variants may contribute to clinical features related to glucose metabolism in Chinese population.

Polymorphism of DsbA-L gene associates with insulin secretion and body fat distribution in Chinese population.

Abstract: Disulfide-bond-A oxidoreductase-like protein (DsbA-L) has been suggested to take part in the disulfide bond formation progress of proteins, including insulin and adiponectin. Recent study has demonstrated that expression of DsbA-L was decreased in obese mice and human subject, indicating that DsbA-L might be a potential target for treatment of metabolic diseases. We investigated the association of SNP-1308G/T (rs1917760) of DsbA-L gene with metabolic diseases. 589 normal glucose tolerance (NGT) subjects and 556 type 2 diabetes (T2DM) subjects were recruited. Each group was divided into normal weight (NW) (BMI‹24 kg/m2) subgroup and overweight/obesity (OW/OB) (BMI≥24 kg/ m2) subgroup. Genotype distributions and allele frequencies of SNP (-1308G/T) in DsbA-L gene were not associated with T2DM and obesity. However, it was observed that T allele carriers had better insulin secretion function compared with non-T allele carriers in NGT-NW group, not only the first phase insulin secretion (P=0.007) but also the second phase insulin secretion (P=0.031). Multiple linear regression analysis revealed that SNP-1308G/T polymorphism (rs1917760) was independently correlated with both first and second phase insulin secretion in NGT-NW group (R2=0.055, P=0.007; R2=0.029, P=0.041). Otherwise, T carriers had more visceral fat than non-T carriers (P=0.020) in NGT-OW/OB group. In conclusion, the SNP-1308G/T (rs1917760) genotypes of DsbA-L gene might participate in insulin secretion and body fat distribution. It is possible that polymorphisms of DsbA-L gene associated with metabolic diseases.

A genetic variant of G6PC2

Abstract: Unfortunately, the authors made a mistake when calculating HOMA-B, and the values reported in Table 3 and ESM Tables 3 and 4 were incorrect by a factor of 20. This mistake does not affect the findings of this study. The corrected version of Table 3 is reproduced here, and the corrected versions of ESM Tables 3 and 4 are available to authorised users. Diabetologia (2009) 52:733 DOI 10.1007/s00125-009-1286-y

Comparison of the application of three diagnostic criteria of metabolic syndrome in familial type 2 diabetic pedigrees

Abstract: Objective To compare the significance of the application of three diagnostic criteria of metabolic syndrome (MS),issued by the National Cholesterol Education Program Adult Treament Panel Ⅲ ( ATPⅢ) in 2005 ,International Diabetes Federation (IDF) in 2005 and Chinese Diabetes Society (CDS) in 2004,in type 2 diabetes mellitus pedigrees. Methods Totally,4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data, including blood pressure, lipid profile and plasma glucose, were collected. The prevalence rates of MS and the unity of three criteria were analyzed. Results The prevalence rates of MS were 44.94% (2008/4468), 37.87% (1692/4468) and 23.86% (1066/4468) according to the ATPⅢ ,IDF and CDS criteria respectively. It subsequently increased in second-degree relatives, spouses, first-degree relatives and probands ( ATPⅢ: 23.78% (117/492), 35.77% (318/889) ,45.40% (1077/2372) and 69.37% (496/715) ; IDF: 20. 53% (101/492) ,31.61% (281/889) ,38.74% (919/2372) and 54.69% (391/715) ; CDS: 8.94% (44/492) ,16.99% (151/889), 25.08% (595/2372) and 38.60% (276/715) ; ATP Ⅲ : X = 266.359, IDF:X = 155.950, EDS : X2 =165.087 ,respectively,P <0.01). The prevalence rates of MS, as defined by the ATP Ⅲ and IDF criteria, were higher in females than in males ( ATP Ⅲ: 47.47% (1156/2435) and 41.91% (852/2033) ; IDF: 43.00% (1047/2435) and 31.73% (645/2033) ; X2=13.871 and 60.169, respectively, P <0.01), and was lower in females than in males as defined by the CDS criterion (22.38% and 25.63% ,respectively, X2= 6.423,P = 0.011). The agreement in the diagnosis of MS using ATP Ⅲ and IDF, ATP Ⅲ and CDS, IDF and CDS was 92.93%, 75.56% and 77.21% respectively. Kappa index were 0.855,0.484 and 0.478 respectively (P<0.01 ). Conclusion ATP Ⅲ criterion showed the highest prevalence of MS and the percent of risk factor aggregation which best reflected the characteristics of MS in familial type 2 diabetic pedigrees. Key words: Metabolic syndrome X; Diabetes mellitus,type 2; Prevalence; Pedigree

Common Variants of Hepatocyte Nuclear Factor 1 Are Associated With Type 2 Diabetes in a Chinese

Abstract: OBJECTIVE Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1β were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1β in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1β gene in a Chinese population. RESEARCH DESIGN AND METHODS Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785). RESULTS Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05–1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228). CONCLUSIONS The result of this study provides evidence that variants in the HNF1β region contribute to susceptibility to type 2 diabetes in the Chinese population.

Prevalence of metabolic syndrome and its relationship with obesity-related indicators in first-degree relatives of familial type 2 diabetes pedigrees

Abstract: Objective To compare the differences of metabolic syndrome (MS) prevalence by using four working definitions and their relationship with obesity-related indicators in first-degree relatives of type 2 diabetes mellitus pedigrees. Methods Totally, 2 372 first-degree relatives from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data, including blood pressure, lipid profile and plasma glucose, were collected. The prevalence rates of MS and obesity of four definitions, as defined by National Cholesterol Education Program Adult Treatment Panel Ⅲ (ATPⅢ) in 2005, International Diabetes Federation (IDF) in 2005,Chinese Diabetes Society (CDS) in 2004 aml Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG) in 2007,were analyzed. Results (1)The prevalence rates of MS were 45.40% ,38.74% ,25.08% and 39.29% aecording to four definitions respectively. The prevalence rates of MS were higher in females than in males by using ATPⅢ and IDF definitions (both P<0. 01). (2)The common comhinations of metabolic abnormality was dyslipidemia, hypertension, obesity and hyperglycemia by using four definitions,except in females by using CDS definition. (3)The prevalence rates of obesity were 58.18% ,58.18% ,33.90% and 42.96% acconling to the four definitions respectively. The prevalence rates of MS in obese subjects were 66.59% ,66.59% ,54.85% and 68.99% according to four definitions respectively. (4) Applying the cutoff point for abdominal obesity according to ATPⅢ, IDF and JCDCG definitions, the prevalence rates of abdominal obesity in subjects with body mass index (BMI) <25 kg/m2 were respectively 28.58% and 16.78%, being higher in females than in males(38.90% vs 15.02% ,21.01% vs 11.22% ,both P<0. 01). Conclusion (1)There is significant familial aggregation of MS and obesity,and the first-degree relatives of type 2 diabetic patients are high risk populations. (2) Waist circumference rather than BMI taken as a discriminating component of obesity in MS seems to be clinically more helpful to the early identification and prevention of MS. Key words: Metabolic syndrome; Obesity; Diabetes mellitus,type 2; Pedigree; Prevlence

Method for detecting rs16856187 polymorphic site on 3' region of G6PC2 gene

Abstract: The invention relates to a method for detecting rs16856187 polymorphic site on 3' region of G6PC2 gene, belonging to the technical field of molecular biology. The method comprises: genome DNA is extracted from samples and is taken as a DNA template; a pair of nucleic acid primers which can specifically amplify production containing 101st nucleotide polymorphism in the sequence shown in SEQ ID NO.1, and target gene is amplified by the pair of primers; rs16856187 polymorphic loci genotype is tested, and whether single nucleotide polymorphism from C to A exists at the 101st position of the sequence shown in SEQ ID NO.1. The invention establishes a method for quickly detecting rs16856187 polymorphic site of the G6PC2 gene in a large batch of samples.