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Aim There is a close link between electrocardiographic ventricular repolarization QT parameters and Type 2 diabetes. The aim of the present study was to assess the effects of QT-related and diabetes-related variants in KCNQ1 on QT interval in a Chinese population. Methods We recruited 2415 patients with Type 2 diabetes and 1163 subjects with normal glucose regulation in the present study. QT interval was obtained and the heart rate-corrected QT interval ( QTc) was calculated using Bazett's formula. Four single nucleotide polymorphisms in KCNQ1 were selected (rs12296050, rs12576239, rs2237892 and rs2237895) and genotyped. Results In participants with normal glucose regulation, the minor allele T of rs12296050 was associated with a 3.46-ms QTc prolongation under an additive model ( P = 0.0109, empirical P = 0.0498). In patients with Type 2 diabetes, we did not find any association for the single nucleotide polymorphisms. Conclusions Our findings indicate that KCNQ1 is associated with QT interval in a Chinese population with normal glucose regulation. [ABSTRACT FROM AUTHOR]

Aims Hepatocyte nuclear factor-1α (HNF-1α) regulates the expression of genes encoding proteins involved in glucose metabolism and insulin secretion. Mutations in the HNF-1α gene cause maturity-onset diabetes of the young Type 3. However, the mechanism leading to this disease has not been completely ascertained. Previously, we found a novel mutation in the regulatory element of the human HNF-1α gene in two Chinese diabetes pedigrees. The nucleotide at position -128 T was substituted by G (nt-128 T→G). In this study, we analysed the functional defect of nt-128 T→G in HNF-1α transcription activity. Methods Luciferase reporter gene assays were carried out to examine the functional characteristics of this mutant. Electrophoretic mobility shift assays and chromatin immunoprecipitation were performed to confirm the binding of nuclear proteins to oligonucleotides. Results The variant construct (nt-128 T→G) had a 1.65-fold increase in promoter activity compared with that of the wild-type construct in HepG2 cells and a 1.33-fold increase in MIN6 cells, respectively. The variant resided at a FOXA/HNF-3 binding site identified by a series of competitive electrophoretic mobility shift assays and antibody supershift analyses. The assays showed a differential binding affinity in the wild-type and the nt-128 T→G mutant fragments by FOXA/HNF-3. Chromatin immunoprecipitation indicated that FOXA/HNF-3 bound to this region in vivo. One nucleotide substitution in the FOXA/HNF-3 site in the human HNF-1α regulatory element caused an increase of HNF-1α transcriptional activity. Conclusions Our data suggested that this substitution in the promoter region affects DNA-protein interaction and HNF-1α gene transcription. The mutant may contribute to the development of diabetes in these two nt-128 T→G pedigrees of Chinese. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 598–602 (2010) Aims To investigate the two variants (rs1387153 and rs10830963) near/in the melatonin receptor 1B gene ( MTNR1B) and to determine their association with Type 2 diabetes, as well as with the regulation of fasting plasma glucose (FPG) in Han Chinese subjects. Methods The two variants were genotyped in 1912 unrelated Type 2 diabetic patients and 2041 healthy individuals. Association with Type 2 diabetes was calculated by logistic regression with adjustments for sex, age and body mass index. The possible connection between the risk alleles and FPG was analysed by multiple linear regression. Results The two polymorphisms were associated with FPG levels in the healthy individuals ( P = 0.003 and P = 0.002, respectively), and the G allele of rs10830963 was also associated with an increased risk of Type 2 diabetes in our patient sample (odds ratio, 1.12; 95% confidence interval, 1.02–1.23; P = 0.024). Moreover, the linkage disequilibrium degree of two single nucleotide polymorphisms was high ( r2 = 0.66), which is similar to that of Europeans. Conclusions The common variant in MTNR1B confers the risk of Type 2 diabetes and modulates FPG in both the Han Chinese and European populations. [ABSTRACT FROM AUTHOR]

Aims To determine the incidence of gestational diabetes mellitus (GDM) in China and to further identify population specific risk factors for GDM. Methods Following a universal GDM screening recommendation, 16 286 pregnant women who underwent a 50-g glucose challenge test from 18 cities in China were followed up through pregnancy. GDM was confirmed by oral glucose tolerance test according to American Diabetes Association criteria. Results The incidence of GDM was 4.3%. Previously reported risk factors for GDM, including advanced maternal age, pre-pregnancy obesity and family history of diabetes, were strongly associated with an elevated GDM risk. Moreover, after the adjustment for the above-mentioned risk factors, a history of recurrent vulvovaginal candidiasis, residency in south China and a history of spontaneous abortion were significantly associated with an increased GDM risk; adjusted odds ratio (OR) [95% confidence interval (95% CI)] were 1.97 (1.39, 2.80), 1.84 (1.59–2.13), and 1.46 (1.12, 1.91), respectively. Conclusions In this large study of GDM in Chinese women, advanced maternal age, pre-pregnancy overweight or obesity and family history of diabetes were confirmed to be risk factors. In addition, a history of recurrent vulvovaginal candidiasis or spontaneous abortion and residency in south China appeared to be novel risk factors in this population. [ABSTRACT FROM AUTHOR]

Abstract Aim Recent studies have shown that the risk of developing coronary heart disease in subjects with ‘isolated low high-density-lipoprotein cholesterol (HDL-C)’ (defined as HDL-C < 0.9 mmol/l and total cholesterol (TC) < 5.2 mmol/l) was similar to those with hypercholesterolaemia. We examined the prevalence of isolated low HDL-C in Hong Kong Chinese and its relationship with insulin resistance and triglyceride (TG) level. Methods Hong Kong Chinese subjects (n = 1493) recruited in a population-based prevalence survey for cardiovascular risk factors were examined. Insulin resistance was calculated using a computer-solved homeostasis model assessment method. Results Of the 1493 subjects, 72 (4.8%) had isolated low HDL-C, in whom half (n = 36) had TG ≥ 1.7 mmol/l and half (n = 36) had TG < 1.7 mmol/l. Compared with the ‘controls’ (subjects with TC < 5.2 mmol/l and HDL-C ≥ 0.9 mmol/l; TC ≥ 5.2 mmol/l and HDL-C < 0.9 mmol/l; or TC ≥ 5.2 mmol/l and HDL-C ≥ 0.9 mmol/l, n = 1421), subjects with isolated low HDL-C and high TG were more obese, had higher plasma glucose, fasting and 2 h plasma insulin concentrations and insulin resistance. Subjects with isolated low HDL-C and TG < 1.7 mmol/l had similar insulin concentrations and insulin resistance, but were more obese than the ‘controls’. Subjects with isolated low HDL-C and high TG also had higher fasting PG, insulin and insulin resistance than those with isolated low HDL-C and low TG. Conclusions In this population-based study, 4.8% of Hong Kong Chinese had isolated low HDL-C, which was closely associated with obesity. The coexistence of high TG suggests an insulin-resistant state. Diabet. Med. 18, 663–666 (2001). [ABSTRACT FROM AUTHOR]