OBJECTIVETo assess the association of glucokinase regulator protein (GCKR) gene polymorphisms and type 2 diabetes (T2D) among ethnic Uygurs from Xinjiang, China.

METHODSOne thousand and six T2D patients and 1004 healthy controls were recruited. The rs780094 genotype of the GCKR gene was determined with a Sequenom Mass ARRAY system.

RESULTSThe distribution of GCKR rs780094 AA, AG and GG genotypes were not statistically different between the two groups (P>0.05). After adjusting confounding factors, an association of rs780094 with T2D was observed in an additive and dominant model (OR=1.181, 95%CI: 1.021-1.366, P=0.025; OR=1.296, 95%CI: 1.043-1.610, P=0.019). The total cholesterol level was higher in AA carriers than GG and GA carriers (P<0.05).

CONCLUSIONThe AA genotype of the GCKR rs780094 polymorphism may increase the risk of T2D among ethnic Uygurs from Xinjiang.

Adaptor Proteins, Signal Transducing ; genetics ; China ; ethnology ; Cholesterol ; blood ; Diabetes Mellitus, Type 2 ; blood ; etiology ; genetics ; Genotype ; Humans ; Logistic Models ; Polymorphism, Genetic

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of susceptibility genes of type 2 diabetes mellitus (T2DM) with liability to gout among ethnic Han Chinese males from coastal region of Shandong province. METHODS Seven SNPs within the susceptibility genes of T2DM, including rs10773971(G/C) and rs4766398(G/C) of WNT5B gene, rs10225163(G/C) of JAZF1 gene, rs2069590(T/A) of BDKRB2 gene, rs5745709(G/A) of HGF gene, rs1991914(C/A) of OTOP1 gene and rs2236479(G/A) of COL18A1 gene, were typed with a custom-made Illumina GoldenGate Genotyping assay in 480 male patients with gout and 480 male controls. Potential association was assessed with the chi-square test. RESULTS No significant difference was detected for the 7 selected SNPs in terms of genotypic and allelic frequencies (P > 0.05). When age and body mass index (BMI) were adjusted, the 7 genetic variants still showed no significant association with gout. CONCLUSION The genotypes of the 7 selected SNPs are not associated with gout in ethnic Han Chinese male patients from the coastal region of Shandong province. However, the results need to be replicated in larger sets of patients collected from other regions and populations.
Adult ; Aged ; China ; ethnology ; Diabetes Mellitus, Type 2 ; genetics ; Ethnic Groups ; Genetic Predisposition to Disease ; Gout ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).

METHODSA 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software.

RESULTSFive polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction.

CONCLUSIONThe C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Case-Control Studies ; China ; ethnology ; Diabetes Mellitus, Type 2 ; blood ; ethnology ; genetics ; Ethnic Groups ; genetics ; Female ; Genetic Variation ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transcription Factors ; genetics

OBJECTIVETo identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM).

METHODSFrom November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed.

RESULTSA total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09).

CONCLUSIONSMicroalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

Albuminuria ; epidemiology ; urine ; Aldehyde Reductase ; genetics ; Asian Continental Ancestry Group ; China ; Cohort Studies ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; ethnology ; genetics ; Diabetic Retinopathy ; drug therapy ; ethnology ; etiology ; genetics ; Female ; Gene Frequency ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Insulin ; administration & dosage ; adverse effects ; therapeutic use ; Logistic Models ; Male ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Risk

OBJECTIVETo assess the association between single nucleotide polymorphisms (SNPs) of mannose-binding lectin 2 gene (MBL2) (rs1800450, rs1800451 and rs11003125) and protein kinase C-beta 1 gene (PRKC beta 1) (rs3700106, rs2575390) with diabetic macroangiopathy in northern Chinese Han population.

METHODSThe samples have included 318 type 2 diabetes mellitus (T2DM) patients and 448 normoglycemic controls. The five SNPs were determined by a Multiplex SnaPshot method. Biochemical indices such as fasting plasma-glucose, triglyceride and total cholesterol were also measured. Linkage disequilibrium and haplotype analysis were carried out for all samples using Haploview 4.2. Additive model was applied to assess the effect of interaction between SNPs and environment factors on macrovascular complications.

RESULTSGenotypic frequencies of rs11003125 have differed significantly between the controls and patients with coronary heart disease and peripheral vascular disease (P=0.024 and 0.004, respectively). The allele frequency of rs11003125 was also statistically significant between the two groups (P=0.014 and 0.001, respectively). Compared with patients without macrovascular complications, the allele frequency of rs11003125 was significantly different in patients with peripheral vascular disease (P=0.031). No significant differences were found between the distribution of the genotype frequency and allele frequencies of other variants. Haplotype analysis indicated that, compared with controls and patients without macrovascular complications, individuals with G allele of rs1800450 and C allele of rs11003125 had a higher risk for macrovascular complications.

CONCLUSIONThe rs11003125 polymorphism located in the promoter region of MBL2 gene is associated with macrovascular complications of T2DM in northern Chinese Han population. G allele of rs1800450 and C allele of rs11003125 may be risk factors for macrovascular complications. There were additive interactive effects for rs11003125 polymorphism (GC+CC) and hypertension, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy on macrovascular complications.

Alleles ; China ; ethnology ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Diabetic Angiopathies ; ethnology ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mannose-Binding Lectin ; genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Protein Kinase C ; genetics ; Protein Kinase C beta

Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Female ; Humans ; KCNQ1 Potassium Channel ; genetics ; Male

INTRODUCTIONType 2 diabetes (T2D) candidate gene: potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) was suggested by conducting a genome wide association study (GWAS) in Japanese population. Association studies have been replicated among East Asian populations; however, the association between this gene and T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of KCNQ1 common variants with type 2 diabetes in Malaysian Malay subjects.

MATERIALS AND METHODSThe KCNQ1 single nucleotide polymorphisms (SNPs): rs2237892, rs2283228, and rs2237895 were genotyped in 234 T2D and 177 normal Malay subjects.

RESULTSThe risk allele of the rs2283228 (A) was strongly associated with T2D (OR = 1.7, P = 0.0006) while the rs2237892 (C) was moderately associated with T2D (OR = 1.45, P = 0.017). The recessive genetic models showed that rs2283228 was strongly associated with T2D (OR = 2.35, P = 0.00005) whereas rs2237892 showed a moderate association with T2D (OR = 1.69, P = 0.01). The haplotype block (TCA), which contained the protective allele, correlated with a protection from T2D (OR = 0.5, P = 0.003). Furthermore, the diplotype (CAA-TCA) that contained the protective haplotype was protected against T2D (OR = 0.46, P = 0.006).

CONCLUSIONThe KCNQ1 SNPs, haplotypes and diplotypes are associated with T2D in the Malaysian Malay subjects.

Adult ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Female ; Genetics, Population ; Haplotypes ; genetics ; Humans ; KCNQ1 Potassium Channel ; genetics ; Malaysia ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population.

METHODSOne thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform.

RESULTSThe frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes.

CONCLUSIONVEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; genetics ; Population Groups ; genetics ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVETo investigate the association of the D358A polymorphism of interleukin 6 receptor( IL6R ) gene with type 2 diabetes mellitus (T2DM) in Hubei Han Chinese.

METHODSThe single nucleotide polymorphism D358A of the IL6R gene was genotyped in 581 T2DM patients and 353 healthy controls. Meta-analysis was used to assess the reported association between the IL6R D358A and T2DM.

RESULTSThe frequencies of CC genotype and C allele of IL6R D358A in the patients were significantly lower than those in controls (CC: 13.4% vs. 20.7%, P=0.003; C: 36.0% vs. 41.8%, P=0.012), with the CC genotype being a protective factor for T2DM (OR=0.595, P=0.003). Logistic regression analysis suggested that the CC genotype was significantly associated with T2DM after adjusted for age, sex, blood pressure and obesity (OR=0.615, 95% CI: 0.407- 0.928, P=0.021). Meta-analysis of 6 studies indicated that there existed genetic heterogeneity, and the CC genotype was associated with lower risk of T2DM (P=0.009, OR=0.64, 95% CI: 0.48-0.85).

CONCLUSIONIL6R is a susceptibility gene for T2DM in Han Chinese population of Hubei, and the CC genotype may serve as a genetic protective factor of T2DM.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; European Continental Ancestry Group ; genetics ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-6 ; genetics

OBJECTIVETo study the genetic determination of fast plasma glucose (FPG) and correlation with its potential correlated traits, anthropometric measures and blood pressure.

METHODSTwo hundred and eighteen Type 2 diabetes mellitus (T2DM) pedigrees composed of 1383 Chinese Han individuals residing in the East and South-East China were analyzed. Univariate variance decomposition analyses were used to estimate the narrow-sense heritability (h(2)) of FPG, anthropometric indices and blood pressure, and bivariate quantitative genetic analyses were used to estimate the genetic and environmental correlations between FPG and anthropometric measures or blood pressure.

RESULTSWe found that FPG, blood pressure and all anthropometric indices except for waist to hip ratio were under significant genetic determination, and the h(2) was from 0.28 to 0.43. We did not find significant genetic and environmental correlation between FPG and anthropometric indices and blood pressure.

CONCLUSIONThe present study demonstrated that T2DM, obesity and hypertension were controlled by some genetic factors, and FPG shares little common genetic and environmental factors with obesity-related anthropometric indices and blood pressure in our Chinese sample population.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anthropometry ; Asian Continental Ancestry Group ; genetics ; Blood Glucose ; genetics ; Blood Pressure ; genetics ; Cardiovascular Diseases ; epidemiology ; genetics ; China ; ethnology ; Diabetes Mellitus, Type 2 ; genetics ; Fasting ; blood ; metabolism ; Female ; Genetic Predisposition to Disease ; Glucose ; genetics ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Obesity ; genetics ; Risk Factors ; Waist-Hip Ratio ; Young Adult