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ABSTRACT: Obesity and family history are the most important predictors for type 2 diabetes mellitus(T2DM) in the Chinese Han population. However, it is not known whether the genetic loci related to obesity are associated with the risk of developing T2DM in this population. The present case-control study evaluated the associations between five genetic loci for obesity and the pathogenesis of T2DM. The study included 1117 Chinese Han patients with T2DM, 1629 patients with pre-diabetes (impaired fasting glucose and impaired glucose tolerance, IFG/IGT) and 1113 control subjects residing in Beijing. Five genetic loci including rs2815752 near NEGR1, rs10938397 near GNPDA2, rs4074134 near BDNF, rs17782313 near MC4R and rs1084753 near KCTD15 were genotyped. The results showed an association between rs4074134-BDNF minor allele and T2DM irrespective of age, gender and body mass index (BMI) (OR = 0.87; 95%CI: 0.77-0.99, P = 0.04). This SNP was also associated with pre-diabetes (OR = 0.87; 95%CI: 0.77-0.97, P = 0.01) independently of age, gender and BMI. No associations were found between diabetes or pre-diabetes and any of the other SNP loci studied. Genotype-phenotype association analysis (adjusting for age and gender) showed rs4074134-BDNF to be associated with BMI, waist circumference, fasting and postprandial plasma glucose, fasting serum insulin, and HOMA-IR in subjects without T2DM. However, fasting and postprandial plasma glucose were the only significant factors after adjusting for BMI. These results suggest that the common variation of BDNF (rs4074134) is associated with T2DM independently of obesity in Chinese Han population. This variant also has an effect on plasma glucose concentration, BMI and insulin sensitivity.
PLoS ONE 01/2013; 8(2):e56898. · 4.09 Impact Factor
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Huaixing Li,
Wei Gan,
Ling Lu,
Xiao Dong,
Xueyao Han,
Cheng Hu,
Zhen Yang,
Liang Sun,
Wei Bao,
Pengtao Li, [......],
Frank B Hu,
Tangchun Wu,
Ying Liu,
Liegang Liu,
Ze Yang,
Renming Hu,
Weiping Jia,
Linong Ji,
Yixue Li,
Xu Lin
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ABSTRACT: Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.
Diabetes 09/2012; · 8.29 Impact Factor
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Yong Tang,
Xueyao Han,
Xiuqin Sun,
Chao Lv,
Xiaomei Zhang,
Wulan Guo,
Qian Ren,
Yingying Luo,
Xiuying Zhang, Xianghai Zhou,
Linong Ji
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ABSTRACT: The insulin receptor substrate-1 (IRS1) plays an important role in insulin signaling. A recent genome-wide association study identified rs2943641C>T as a susceptibility locus for type 2 diabetes mellitus (T2DM) in Caucasian patients. Therefore, we determined whether this common variant near IRS1 is also associated with the risk of T2DM and T2DM-related phenotypes in a Chinese Han population. A total of 2,290 unrelated Chinese Han individuals residing in Beijing were recruited in this study, including 1177 T2DM patients and 1113 subjects with normal glucose tolerance (control group). The single nucleotide polymorphism (SNP) was genotyped using a MassARRAY iPLEX system. The frequency of risk allele C was 0.929 in the control group and 0.939 in patients with T2DM. We found no association between the C allele of rs2943641 and T2DM in a recessive model [OR 1.14, 95 % confidence interval (CI) 0.89-1.45, P = 0.298], or after adjusting for sex, age, and body mass index (BMI) (OR 1.10, 95 % CI 0.85-1.43, P = 0.301). Analysis of the clinical features of the control subjects with normal glucose tolerance revealed that the 30-min plasma glucose level during a 75-g oral glucose tolerance test was significantly different between the CC and CT+TT genotypes (P = 0.017). Linear regression analysis showed that the 30-min plasma glucose levels was significantly and positively associated with the CC genotype after adjusting for sex, age, and BMI (β = 0.065, 95 % CI 0.009-0.654, P = 0.044). In addition, a potential association between this SNP and increased waist circumference (β = 1.337, 95 % CI -0.179 to 2.853, P = 0.084) was observed with adjustment for the sex and age. Our study was not able to demonstrate the association between rs2943641 near IRS1 and T2DM in a Chinese Han population. However, this SNP may be associated with postprandial hyperglycemia.
Endocrine 05/2012; · 1.42 Impact Factor
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ABSTRACT: A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093-1.188), 1.177 (1.099-1.259) and 1.207 (1.094-1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.
Molecular Biology Reports 05/2011; 39(1):645-59. · 2.93 Impact Factor
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ABSTRACT: To investigate the association of fresh vegetable consumption with the risk of diabetes in a Chinese population.
Data from 2386 individuals aged 35-74 years who participated in a population-based cross sectional diabetes survey in Qingdao, China were analyzed. Frequency of vegetable intake was obtained using a food frequency questionnaire. Diabetes was defined as self-reported diabetes or undiagnosed diabetes determined by 2-h 75 g oral glucose tolerance test or fasting capillary blood glucose test. Multivariate-adjusted odds ratio (OR) for the presence (vs. the absence) of diabetes in association with the frequency of fresh vegetable intake was estimated using logistic regression analysis.
The OR for the presence of diabetes was 1.17 (95% CI 0.66, 2.05) in men and 0.50 (95% CI 0.33, 0.77) in women who ate fresh vegetables more than 14 times/week as compared with those who ate fresh vegetables less than 7 times/week after adjustment for age, family history of diabetes, BMI, systolic blood pressure, 24-h energy intake, physical activity and smoking and drinking.
Consumption of fresh vegetables was associated with a low risk of having diabetes in women but not in men in this Chinese population.
Diabetes research and clinical practice 03/2011; 92(1):137-42. · 2.16 Impact Factor
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ABSTRACT: Recently, several genome-wide and candidate gene association studies have identified many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important. We aimed to determine the effects of these genetic loci associated with T2D in the Chinese Han population of China.
Single-nucleotide polymorphisms (SNPs) in or near CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 genes were genotyped in a case-control Chinese Han sample living in Beijing, China involving 1024 patients with T2D and 1005 control subjects.
In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 x 10(-4)) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index. Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis. Moreover, the relationship between FTO-rs8050136 and body mass index, together with the effect of CDKAL1-rs10946398 on beta cell function, was also observed in the control individuals.
Our findings support the important contribution of these genetic loci to susceptibility for T2D in the Chinese Han population in Beijing of China.
BMC Medical Genetics 01/2010; 11:81. · 2.33 Impact Factor
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ABSTRACT: OBJECTIVE The study's goal was to evaluate the performance of A1C and fasting capillary blood glucose (FCG) tests as mass screening tools for diabetes and pre-diabetes, as determined by the standard oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Data from 2,332 individuals aged 35-74 years who participated in a population-based cross-sectional diabetes survey in Qingdao, China, were analyzed. A 2-h 75-g OGTT was used to diagnose diabetes. The performance of A1C and FCG was evaluated against the results of the OGTTs by using receiver operating characteristic curve (ROC) analysis. RESULTS The prevalence of newly diagnosed diabetes and pre-diabetes (impaired fasting glucose and/or impaired glucose tolerance) was 11.9 and 29.5%, respectively. For subjects with newly diagnosed diabetes, the area under the ROC curve was 0.67 for A1C and 0.77 for FCG (P < 0.01) in men and 0.67 and 0.75 (P < 0.01) in women, whereas for pre-diabetes, these values were 0.47 and 0.64 (P < 0.001) in men and 0.51 and 0.65 (P < 0.001) in women. At the optimal A1C cutoff point of > or =5.6% for newly diagnosed diabetes, sensitivities (specificities) were 64.4% (61.6%) for men and 62.3% (63.3%) for women. CONCLUSIONS As a screening tool for newly diagnosed diabetes and pre-diabetes, the FCG measurement performed better than A1C in this general Chinese population.
Diabetes care 12/2009; 33(3):545-50. · 8.09 Impact Factor
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ABSTRACT: To identify risk factors associated with the presence of diabetes.
A diabetes survey was conducted in 2801 citizens aged 35-79 years living in 10 communities in Beijing, China. Participants were recruited by residents committees. 75g oral glucose tolerance test was performed to define diabetes according to the WHO 1999 criteria. Logistic regression analysis was used to estimate odds ratios (OR) for diabetes.
The prevalence of diabetes and impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was 24.2% and 20.4% in men, respectively and 19.4% and 19.0% in women, respectively. The multivariate adjusted OR (95% CI) corresponding to a one standard deviation increase in age (year) was 1.52 (1.25,1.86), waist circumference (cm) 1.35 (1.12,1.63), serum triglycerides (mmol/L) 1.29 (1.09,1.54) and high density lipoprotein cholesterol (mmol/L) 0.74 (0.61,0.91) in men and 2.03 (1.77,2.33), 1.21 (1.06,1.38), 1.34 (1.21,1.49), 0.74 (0.66,0.84) in women, respectively. For diabetes family history they were 2.46 (1.66,3.65) in men and 2.39 (1.84,3.10) in women, and for hypertension 1.14 (0.77,1.68) in men and 1.54 (1.18,2.01) in women. There were no significant associations between the presence of diabetes and occupation, education level, household income, leisure time physical activities, current smoking and drinking status.
Age, diabetes family history, obesity, dyslipidemia and hypertension were all associated with the presence of diabetes in this study population.
Diabetes research and clinical practice 12/2009; 86(3):233-8. · 2.16 Impact Factor
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ABSTRACT: Understanding the metabolic basis of glucose intolerances and insulin resistance is essential to facilitate early diagnosis, satisfactory therapies and personalized treatments of type 2 diabetes (T2DM). Here, we analyzed the serum metabolic variations from 231 human participants with normal glucose tolerance (NGT, n = 80, M/F = 34/46, mean age 53 +/- 10 years), impaired glucose regulation (IGR, n = 77, M/F = 33/44, mean age 51 +/- 10 years) and T2DM (n = 74, M/F = 32/42, mean age 51 +/- 9 years) to establish the relationship between the serum metabolite compositions and the development of diabetes. By using the proton nuclear magnetic resonance spectroscopy in conjunction with the multivariate data analysis, we found that the development of both glucose intolerances and insulin resistances are closely correlated with the progressive changes of human serum metabonome. Compared with NGT subjects, the IGR and T2DM participants showed clear dysfunctions of choline metabolism, glucose metabolism, lipid and amino acid metabolisms, and disruptions of TCA cycle. The insulin resistance statuses were closely associated with the serum metabonomic changes in terms of glucose, fatty acid and protein/amino acid metabolisms. We also found greater metabonomic heterogeneity among the populations with T2DM and high insulin resistance status. These findings provide useful information to bridge the gaps in our understandings to the metabolic alterations associated with the progression of glucose intolerances and insulin resistance status.
Journal of Proteome Research 09/2009; 8(11):5188-95. · 5.11 Impact Factor
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ABSTRACT: To evaluate the effect of TCF7L2 on genetic susceptibility of type 2 diabetes (T2DM) in East Asian population by using the meta-analysis.
Search all the publications about the association between TCF7L2 and T2DM in East Asian population from PubMed, CNKI and abstracts of major diabetes conferences. Perform the meta-analysis of all the validated studies and evaluate the association between rs7903146 T allele, rs12255372 T allele, rs11196205 C allele, rs290487 C allele and rs11196218 G allele of TCF7L2 and the risk of T2DM.
Eleven studies from nine eligible papers and one unpublished study of ours were included in the meta-analysis. Ten eligible studies were analyzed for rs7903146, five were analyzed for rs12255372 and rs11196205, and three were analyzed for rs290487 and rs11196218. We found that four SNPs (rs7903146, rs12255372, rs11196205, rs290487) in TCF7L2 were significantly associated with T2DM in East Asian populations. The rs11196218 also showed a marginal association. The estimated population-attributable risk (PAR) associated with analyzed SNPs ranged from 2% to 7%.
SNPs in TCF7L2 were strongly associated with the risk of T2DM in East Asian population. But the contribution of its genetic variants to the epidemic of type 2 diabetes in East Asian was relatively low.
Diabetes research and clinical practice 06/2009; 85(2):139-46. · 2.16 Impact Factor
