- Polymorphism of the Uncoupling Protein 1 (UCP-1) Gene and Fatty Acid Binding Protein 2 (FABP2) Gene in Korean Type 2 Diabetic Patients.
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Sun Gyu Kim, Chul Hee Kim, Seog Ki Yun, Yeo Il Yun, Yong Hyun Kim, Il Song Nam, Ju Young Lee, Ji O Mok, Hyeong Kyu Park, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo
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Korean Diabetes J. 2001;25(4):262-272. Published online August 1, 2001
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Abstract
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- BACKGROUND
It is well known that genetic component plays an important role in developing obesity and type 2 diabetes mellitus. A number of candidate genes have been suggested, but the major gene determining the development of obesity and type 2 diabetes has not yet been uncovered. Previous studies suggest that polymorphisms of the intestinal fatty acid binding protein (FABP2) and uncoupling protein 1 (UCP-1) gene were related with obesity and/or insulin resistance in several populations. METHODS: We examined 76 type 2 diabetic patients (aged 44+/-6 years) and 96 healthy controls (aged 25+/-3 years). Ala54Thr polymorphism of the FABP2 gene and A to G polymorphism (-3826) of the UCP-1 gene were determined by polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: The Thr54 allele of the FABP2 gene was found with a frequency of 0.33 in nondiabetic controls and 0.36 in type 2 diabetic patients. The genotype frequency of the Ala54Thr polymorphism was similar in nondiabetic and diabetic subjects ( 2=0.87, P=0.64). The -3826 G allele of UCP-1 gene was found with a frequency of 0.51 in nondiabetic controls, and 0.46 in type 2 diabetic patients. The genotype frequency of the -3826 A to G polymorphism was also similar in nondiabetic and diabetic subjects ( 2=1.46, p=0.46). When the subjects of each groups were subdivided into nonobese and obese group by BMI of 25 kg/m2, there was no significant difference in genotype frequencies of the UCP-1 and FABP2 gene polymorphisms. CONCLUSION: These results suggest that either the Ala54Thr polymorphism of the FABP2 gene or the A to G polymorphism (-3826) of UCP-1 gene do not play a major role in developing type 2 diabetes mellitus or obesity in Korean.
- Association Between Uncoupling Protein-1 and 3-adrenergic Receptor Gene Polymorphisms and Energy Metabolism in normal Korean Adults.
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Jae Han Kim, Seog Ki Yun, Chul Hee Kim, Dong Won Byun, Young Sun Kim, Kyo Il Suh, Myung Hi Yoo
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Korean Diabetes J. 1999;23(6):803-813. Published online January 1, 2001
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Abstract
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- BACKGROUND
The beta3-adrenergic receptor (beta3-AR) and uncoupling protein 1 (UCP-1), expressed mainly in brown adipose tissue, are involved in the regulation of thermogenesis and lipolysis. Recent studies have shown that polymorphisms of the 3-AR (Trp64Arg) and UCP-1 (-3826, A to G) genes are associated with low basal metabolic rate (BMR) and obesity. METHODS: We investigated the effects of the beta3- AR and UCP-1 gene polymorphisms on body fat and energy metabolism in 65 normal Korean men aged from 21 to 36 years. The Trp64Arg mutation of the beta3-AR gene and A to G polymorphism (-3826) of UCP-1 gene were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. RESULT: In normal Koreans, Arg64 allele frequency of the beta3-AR was 0.15 and the allele frequency of the A to G substitution of the UCP-1 gene was 0.48. No significant difference was found in BMR, body fat and abdominal fat amount in relation to beta3-AR or UCP-1 genotypes. However, when the polymorphisms of the two genes were combined, the subjects with the polymorphisms of both UCP-1 and g-AR genes were found to have higher body mass index, higher total fat and abdominal fat amount, lower BMR, and lower fat oxidation rate when compared with the subjects without these polymorphisms. CONCLUSION: These results suggest that the polymorphisms of either beta3-AR or UCP-1 gene alone did not significantly affect BMR, fat oxidation and body fat amounts, but both UCP-1 and beta3-AR genes polymorphisms have synergistic effects on decreased basal metabolic rate, fat oxidation rate, and increased body fat in normal Korean adults.
- Association between FABP2 Gene Polymorphism and Energy Metabolism in Normal Korean.
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Seog Ki Yun, Chul Hee Kim, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Guk Bae Kim
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Korean Diabetes J. 1998;22(4):457-466. Published online January 1, 2001
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Abstract
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- BACKGROUND
The human intestinal fatty acid binding protein (FABP2) locus has been proprosed to be a major candidate gene in determining insulin resistance. It has been hypothesized that alanine to threonine substitution at codon 54 (Ala54Thr) of the FABP2 gene may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. FABP2 polymorphism was recently shown to be associated with insulin resistance in several populations including Mexican-Americans, Pima Indians, and Japanese, but not associated in the English, Wales, and Finn. METHODS: We investigated the association ot the FABP2 gene polymorphism and insulin resistance, fat absorption, and body fuel metabolism in 96 normal Korean men aged between 21 and 36 years. RESULTS: In normal Koreans, the alanine-encoding allele frequency was 0.66 and threonine encoding allele frequency was 0.34. Subjects with threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a higher insulin resistance index, and a higher basal fat oxidation rate compared with subjects who were homozygous for the alanine-encoding allele. CONCLUSION: These results show that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and insulin resistance in normal Korean men.
- Soluble P-selectin, E-selectin, and VCAM-1 as Markers of Vascular Endothelial Damage in Diabetic Patients with Microangiopathy.
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Young Sun Kim, Dong Won Byun, Kyo Il Seo, Myung Hi Yoo, Guk Bae Kim, Seong Soo Koong
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Korean Diabetes J. 1998;22(1):35-46. Published online January 1, 2001
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Abstract
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- BACKGROUND
Vascular complications of diabetic patients are common and are known as the major cause of death. Hyperglycemia has been supposed to be the leading cause of vascular complications by unknown mechanisms. In recent reports, hyperglycemia stimulated the expression of leukocyte-endothelial adhesion molecules in the endothelial cells, and increased plasma concentrations of their soluble forms. The aim of this study was to evaluate the role of plasma concentrations of soluble P-selectin(sP-selectin), soluble E-selectin(sE-selectin), and soluble VCAM-1(sVCAM-1) in diabetic patients with microvascular complications as markers of vascular endothelial damage. METHODS: In this study, plasma levels of sP-selection, sE-selectin and sVCAM-1 were determined by ELISA in 39 diabetic patients and 25 normal conirols. RESULTS: The concentrations of sP-selectin, sE-selectin, and sVCAM-1 in diabetic group were significantly higher than those in control group. The concentrations of sP-selectin and sE-selectin decreased sigruficantly after contol of hyperglycemia in diabetic group, but sVCAM-1 level was not altered by treatment. In diabetic group with microvascular complications, the concentrations of sP-selectin and sE-selectin significantly were elevated as compared with the diabetic group without microvascular complication, but the concentration of sVCAM-l was not different between the two groups. In diabetic group, the levels of sP-selectin, sE-selcctin, and sVCAM-1 were not correlated with the concentration of C-peptide, HbA1, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol. There was no difference between control group and diabetic group in terms of age and sex. There were not any differences of sP-selectin, sE-selectin, and sVCAM-1 concentration according to the duration of diabetes and the presence of hypertension. CONCLUSION: Hyperglycemia might stimulated the expression of P-selectin, E-selectin, and VCAM-1 in the endothelial cells and increased the plasma levels of their soluble forms. sP-selectin and sE-selectin could be used as indicators of ongoing vascular dysfunction in diabetes as well as a dynamic surrogate marker for the effectiveness of therapeutic interventions.
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