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 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

Type 2 diabetes is characterized by insulin resistance, and ENPP1 plays an important role in insulin resistance. We investigated the association of the ENPP1 K121Q polymorphism with both diabetes and obesity (body mass index [BMI]) in Korean male workers. The study design was case-control. Subjects were 1,945 male workers (type 2 diabetes, 195; non-diabetes, 1,750) of nuclear power plants who received examinations from March to October in 2004. We collected venous blood samples under fasting (> or =8 hr) conditions, calculated BMI by height and weight, and assessed relevant biochemical factors. The results of this study demonstrated that the ENPP1 121Q genotype (KQ+QQ types) was not associated with type 2 diabetes (odds ratios [OR], 0.854; 95% confidence interval [CI], 0.571-1.278) or obesity (OR, 0.933; 95% CI, 0.731-1.190). In addition, the frequency of the Q allele was not related to type 2 diabetes (OR, 0.911; 95% CI, 0.630-1.319) or obesity (OR, 0.962; 95% CI, 0.767-1.205). We concluded that the ENPP1 121Q allele is not a critical determinant for either diabetes or obesity in Korean males. The discordance between the results of this study and those derived from studies of Dominican, South Asian, Caucasian, Finnish, and French populations might be due to differences in genetic backgrounds between these populations.
Adult ; Diabetes Mellitus, Type 2/*ethnology/*genetics ; Employment ; Gene Frequency ; Genetic Predisposition to Disease/ethnology ; Genotype ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Obesity/*ethnology/*genetics ; Phosphoric Diester Hydrolases/*genetics ; Polymorphism, Genetic ; Prevalence ; Pyrophosphatases/*genetics

BACKGROUNDCalpain-10 (CAPN10) has been identified as a susceptibility gene in type 2 diabetes mellitus (T2DM) and insulin resistance. The present study aimed to identify the effects of genetic variations in the CAPN10 gene on the development of type 2 diabetes and hypertension in northern Han Chinese population.

METHODSWe performed a case-control study and genotyped single nucleotide polymorphism (SNP)-44, -43, -19 and -63 of CAPN10 gene in 1046 subjects from the northern China, including 493 patients with T2DM and hypertension and 553 age- and gender-matched normal healthy controls.

RESULTSUnivariate analysis showed that the four polymorphisms were not independently associated with T2DM and hypertension. However, the frequency distributions of SNP-44 allele C (allele 2) (17.89% vs 9.80%, P = 0.0016) and genotype CC (22) (4.21% vs 1.01%, P = 0.0059) in obese patients (body mass index > or = 30 kg/m2) were different from those in non-obese patients. Logistic regression analyses revealed that carriers of the 1112/1221 diplotype had a significantly lower odds ratio for diabetes and hypertension (OR = 0.399, 95% CI, 0.196 - 0.814, P = 0.0115). The 1112/1121 diplotype associated with significantly increased risk of type 2 diabetes in Mexican-American was not associated with the increased risk in Chinese.

CONCLUSIONThese results suggested that CAPN10 gene variations might play roles in the risk of diabetes and hypertension in northern Han Chinese population.

Adult ; Aged ; Calpain ; genetics ; China ; ethnology ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Hypertension ; ethnology ; genetics ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci

Non-insulin dependent diabetes mellitus is often associated with some complications such as nephropathy, retinopathy and neuropathy. Genes of the renin angiotensin system are potential candidate genes for diabetic complications. We investigated the relationship between angiotensin converting enzyme (ACE) gene polymorphism in type 2 diabetic patients with and without diabetic nephropathy. Seventy five patients (25 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy) and 37 healthy controls were studied. Gene polymorphism of ACE was determined by PCR (polymerase chain reaction) amplification using allele-spesific primers. The frequencies of ACE DD, ID and II genoypes among the patients with type 2 diabetic patients were found 48%, 42%, 10% whereas in control subjects, 27%, 60%, 13% respectively. Type 2 diabetic patients carrying DD genotype without nephropathy increased 1.77 fold than control subjects (P < 0.05). There is no significant correlation between diabetic nephropathy and ACE gene polymorphism. But we found that ACE DD genotype increased significantly in type 2 diabetic patients compared to control subjects (P < 0.05).
Adult ; Diabetes Mellitus, Type 2/ethnology/*genetics/metabolism ; Female ; Gene Frequency ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/*genetics ; *Polymorphism, Genetic ; Research Support, Non-U.S. Gov't ; Turkey

OBJECTIVETo investigate the distribution of single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China.

METHODSCAPN10 gene was sequenced to detect SNPs in different nationalities of China. Five SNPs were chosen to perform case-control study and haplotype analysis in 156 normal Han people of Northern China and 173 type 2 diabetes. One SNP was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 people).

RESULTSA total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp. The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese were different from those reported in Mexican American. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control, and the haplotype frequencies in the two groups were not significantly different. No positive results was found in TDT and STDT analysis.

CONCLUSIONSThe SNP distribution of CAPN10 gene differs in different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.

Calpain ; genetics ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Ethnic Groups ; Genetic Predisposition to Disease ; Humans ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

Asian Continental Ancestry Group ; China ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Genetic Variation ; Genotype ; Humans ; Insulin Receptor Substrate Proteins ; Intracellular Signaling Peptides and Proteins ; Phosphoproteins ; genetics

OBJECTIVETo investigate the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes mellitus in Yunnan Hans.

METHODSPolymerase chain reaction-sequence specific primers(PCR-SSP) genotyping method was conducted in 108 Han patients with type 2 diabetes and 56 ethnically matched controls from the same area of Yunnan Province.

RESULTSHLA-DQA1*0301(RR=3.092, P<0.01) and DQA1*0501 (RR=3.257, P<0.05) allelic frequencies in type 2 diabetic patients were significantly higher than those in non-diabetic control subjects respectively. HLA-DQA1*0401 (RR=0.371, P<0.01) allelic frequencies in patients were significantly decreased, compared with controls; HLA-DQA1*0302 (RR=3.356, P<0.01) allelic frequencies in patients with type 2 diabetic nephropathy were significantly increased.

CONCLUSIONHLA-DQA1*0301 and DQA1*0501 are susceptible genes of type 2 diabetes in Yunnan Han nationality; in reverse, HLA-DQA1*0401 is a resistant gene. HLA-DQA1*0302 is a susceptible gene of type 2 diabetic nephropathy.

Adult ; Aged ; Aged, 80 and over ; Alleles ; China ; ethnology ; Diabetes Mellitus, Type 2 ; genetics ; Female ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

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