Kuan-Ching Lee

Association Study of the Genetic Polymorphisms of the Transcription Factor 7-Like 2 (TCF7L2) Gene and Type 2 Diabetes in the Chinese Population

OBJECTIVE—Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene is one of the few validated genetic variants with large effects on the risk of type 2 diabetes in the populations of European ancestry. In this study, we aimed to explore the effect of the TCF7L2 polymorphisms in a Han Chinese population. RESEARCH DESIGN AND METHODS—We genotyped 20 single nucleotide polymorphisms (SNPs) across the TCF7L2 gene in 1,520 unrelated subjects from a Han Chinese population in Taiwan. The associations of SNPs and haplotypes with type 2 diabetes and linkage disequilibrium (LD) structure of the TCF7L2 gene were analyzed. RESULTS—The previously reported SNPs rs7903146 T- and rs12255372 T-alleles of the TCF7L2 gene were rare and were not associated with type 2 diabetes in a Chinese population, which may attribute to the low frequencies of these two SNPs. SNP rs290487 located in an LD block close to the 3′ end of the gene was associated with type 2 diabetes (allele-specific P = 0.0021; permuted P = 0.03). The odds ratio was 1.36 for the CT genotype (95% CI 1.08−1.71; P = 0.0063) and 1.51 for the CC genotype (1.10 −2.07; P = 0.0085) compared with the TT genotype, corresponding to a population attributable risk fraction of 18.7%. The haplotypes composed of rs290487 were also significantly associated with type 2 diabetes (global P = 0.012). CONCLUSIONS—We identified a novel risk-conferring genetic variant of TCF7L2 for type 2 diabetes in a Chinese population. Our data suggested that the TCF7L2 genetic polymorphisms are major determinants for risk of type 2 diabetes in the Chinese population.

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population

Vitamin D and its receptor have been suggested to play a role in the pathogenesis of type 1 diabetes mellitus. We have therefore studied the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes, and rates of glutamic acid decarboxylase (GAD65) autoantibody and islet cell autoantibody (ICA512) positivity.

Adiponectin mRNA levels in the abdominal adipose depots of nondiabetic women

BACKGROUND: The human adiponectin gene has been implicated in the pathophysiology of obesity, type II diabetes mellitus, dyslipidemia and atherosclerosis. Investigation of the physiological functions of the adiponectin gene in humans was mainly conducted at the levels of plasma proteins or DNA polymorphisms. The depot-specific adiponectin mRNA levels also could be relevant to these physiological functions.OBJECTIVES: The relation between the adipose depot-specific adiponectin mRNA expression levels and various metabolic factors, including BMI, fasting plasma glucose, insulin, triglycerides (TGs) and HDL-cholesterol and insulin resistance index by HOMA, was investigated among 66 nondiabetic women using quantitative real-time PCR.RESULTS: The subcutaneous relative adiponectin mRNA levels (SRAmR) correlated significantly with the omental relative adiponectin mRNA levels (ORAmR) (γ=0.468, P=0.0001). The SRAmR correlated inversely with the fasting plasma glucose with a borderline significance (γ=−0.35, P=0.058). On the other hand, the ORAmR correlated negatively with serum TG levels with the adjustment for age (γ=−0.33, P=0.007) or age plus BMI (γ=−0.27, P=0.027).CONCLUSION: These results indicate that the adiponectin mRNA levels in different adipose depots were at least related to certain phenotypes of metabolic syndrome. The expression levels of adiponectin in the omental adipose depots are related to TG metabolism.

The Arg16Gly polymorphism of human β2‐adrenoreceptor is associated with type 2 diabetes in Taiwanese people

objective  The significance of the association of amino terminal polymorphisms in β2‐adrenoreceptor (ADRB2) with obesity and type 2 diabetes is controversial and differs among ethnic groups. In this study, the association of ADRB2 with risk and age of onset of type 2 diabetes has been examined in a Taiwanese population.

The Associations of LPIN1 Gene Expression in Adipose Tissue With Metabolic Phenotypes in the Chinese Population

The LPIN1 gene, encoding lipin‐1 protein, plays critical roles in adipocyte differentiation and lipid metabolism. This study aimed to analyze the association of LPIN1 mRNA levels in human adipose tissue with metabolic phenotypes. We also examined the association of LPIN1 genetic variation with type 2 diabetes and related metabolic phenotypes in the Chinese population. The relative LPIN1 mRNA levels were measured in abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) obtained from 102 nondiabetic Chinese females. Seven single‐nucleotide polymorphisms (SNPs) spanning from the 5′‐upstream region to the 3′‐end of the LPIN1 gene were genotyped in 1,520 Chinese (760 type 2 diabetic cases and 760 controls). LPIN1 mRNA levels in VAT were negatively correlated with BMI (r = −0.21, P = 0.03), body fat percentage (r = −0.22, P = 0.02), plasma triglycerides levels (r = −0.21, P = 0.03), and plasma leptin levels (r = −0.63, P = 0.0002). LPIN1 mRNA levels were positively correlated with PPARG and ADIPOQ mRNA levels in both VAT and SAT. No single SNP of the LPIN1 gene was associated with type 2 diabetes in our population. One rare haplotype showed a significant association with type 2 diabetes (odds ratio (OR), 4.35; 95% confidence interval, 1.86–11.75; P = 4 × 10−4). No SNP or haplotype of the LPIN1 gene was associated with quantitative metabolic traits in the nondiabetic subjects. The results confirmed the association of LPIN1 gene expression in adipose tissue with lower adiposity and favorable metabolic profiles in the Chinese population. However, the LPIN1 gene seemed not to be a major susceptibility gene for type 2 diabetes or related metabolic phenotypes in the Chinese population.

Expression of subcutaneous adipose tissue phosphoenolpyruvate carboxykinase correlates with body mass index in nondiabetic women

Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme for glyceroneogenesis in adipose tissues. Dysregulated glyceroneogenesis is associated with abnormal fatty acid homeostasis, obesity, and insulin resistance in both animal and cellular studies. However, the role of PEPCK expression in human adipose tissues on metabolic phenotypes has not been explored. This study aimed to analyze the correlation between PEPCK messenger RNA (mRNA) expressions in the subcutaneous adipose tissues with obesity-related metabolic phenotypes. We obtained the demographic data, biochemical variables, and abdominal subcutaneous adipose tissue from 75 nondiabetic nonmenopausal women. The relative PEPCK mRNA levels were quantified by real-time polymerase chain reaction normalized with beta-actin as a control. The PEPCK mRNA levels of subcutaneous tissue were positively correlated with body mass index (BMI) using either univariate (r = 0.413, P < .001) or multivariate linear regression analysis (beta = .978 +/- .239, P < .001). The mRNA expression of PEPCK was also positively correlated with body fat percentage (r = 0.436, P < .001), plasma triacylglycerol, and total cholesterol levels (both P values < .001). However, the significant correlation between lipid profile and PEPCK expression in subcutaneous tissue was abolished after adjusting for BMI. The relative subcutaneous PEPCK mRNA level was not correlated with fasting plasma glucose and insulin, and with an insulin resistance index measured with homeostasis model assessment. In conclusion, we showed that PEPCK mRNA expression in the subcutaneous adipose tissues was associated with BMI and plasma triacylglycerol and total cholesterol levels, but was not correlated with insulin resistance index.

Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjects.

Aim  Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population.

Screening for the Gly40Ser mutation in the glucagon receptor gene among patients with type 2 diabetes or essential hypertension in Taiwan.

As a major counterregulatory hormone of insulin, glucagon plays an important role in regulating glucose homeostasis through its binding to the glucagon receptor. Recently a missense mutation in the glucagon-receptor gene (Gly40Ser) was found to be associated with type 2 diabetes in France and Sardinia, with a frequency as high as 4.6% and 8.3%, respectively. This mutation was also found to be associated with essential hypertension in the white population with a frequency of 5.4%. To investigate the role of this mutation in the pathogenesis of type 2 diabetes and essential hypertension in Taiwanese population, we screened 121 normal controls, 213 unrelated subjects with type 2 diabetes, and 107 unrelated subjects with essential hypertension by use of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). None of the Taiwanese subjects recruited in the study had this receptor mutation. Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.