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

OBJECTIVETo investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han Chinese.

METHODSAn A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTSA highly significant increase in the frequency of the G allele was seen in patients with type 1 diabetes compared with controls (66.1 % vs. 34.7%, respectively; P < 0.0005; OR = 3.670) . This reflected an increase in the GG genotype in patients (48.4% vs. 22.2%, respectively; P =0.025; OR =3.281) and a significant decrease in the AA genotype (16.1 % vs. 52.8%, respectively; P = 0.002). The allele frequencies of A and G in patients with type 2 diabetes were not significantly different from controls(A/G, 50.0/50.0% vs. 65.3/34.7%; P = not significant) . The distribution of genotype, however, differed significantly. This difference reflected an increase in the AG genotype in patients (54.8% vs.25.0%, respectively; P=0.012; OR=3.643) and a decrease in the AA genotype (22.6% vs. 52.8%, respectively; P=0.011).

CONCLUSIONSCTLA-4 49 AA is protective from diabetes mellitus, whereas, CTLA-4 49 G allele (both as homozygotes and as heterozygotes ) confers an increased risk of diabetes mellitus.

Abatacept ; Antigens, CD ; Antigens, Differentiation ; genetics ; CTLA-4 Antigen ; China ; ethnology ; Diabetes Mellitus ; genetics ; Humans ; Immunoconjugates ; Polymorphism, Genetic

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

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

OBJECTIVETo obtain the polymorphic data of short tandem repeat(STR) loci of D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the association of these four STR loci with insulin-dependent diabetes mellitus(IDDM).

METHODSThe polymorphisms of the four STRs were studied by polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients with IDDM.

RESULTSSeven alleles at D15S657 locus, 5 alleles at D11S1369 locus, 7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and allele A(4) at D6S2420 locus were increased significantly in patients with IDDM, compared to those in the control group.

CONCLUSIONThe four STRs, used as genetic markers, were suitable for case-control study, forensic medicine identification and population genetic study. There is an association between the polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.

Adult ; Aged ; China ; ethnology ; Diabetes Mellitus, Type 1 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Tandem Repeat Sequences

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

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

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P = 0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P = 0.008), epidermal growth factor receptor (EGFR, P = 0.003), paired box 4 (PAX4, P = 0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P = 0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.
Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase/genetics ; Alleles ; Asian Continental Ancestry Group/ethnology/genetics ; Cardiovascular Diseases/ethnology/*genetics ; Diabetes Mellitus/ethnology/*genetics ; Female ; Genetic Markers/genetics ; Haplotypes ; Homeodomain Proteins/genetics ; Humans ; Korea ; Longevity/*genetics ; Male ; Middle Aged ; Neoplasms/ethnology/*genetics ; Paired Box Transcription Factors/genetics ; *Polymorphism, Genetic ; Proprotein Convertase 1/genetics ; Receptor, Epidermal Growth Factor/genetics ; Sex Factors ; src-Family Kinases/genetics

OBJECTIVETo investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus.

METHODSAll ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees.

RESULTSFive mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes.

CONCLUSIONTCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus ; ethnology ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Male ; Mutation ; Polymerase Chain Reaction

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