Diabetes & Metabolism Journal

Original Articles

Polymorphism of the Uncoupling Protein 1 (UCP-1) Gene and Fatty Acid Binding Protein 2 (FABP2) Gene in Korean Type 2 Diabetic Patients.: 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; Korean Diabetes J. 2001;25(4):262-272. Published online August 1, 2001

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Abstract PDF: 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.: Jae Han Kim, Seog Ki Yun, Chul Hee Kim, Dong Won Byun, Young Sun Kim, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 1999;23(6):803-813. Published online January 1, 2001

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Abstract PDF: 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.: Seog Ki Yun, Chul Hee Kim, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Guk Bae Kim; Korean Diabetes J. 1998;22(4):457-466. Published online January 1, 2001

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Abstract PDF: 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.

The Significance of thebeta3 Adrenergic Receptor Gene Polymorphism in Obese Koreans.: Byoung Joon Kim, Sung Hoon Kim, Dong Jun Kim, Jong Ryeal Hahm, Jin Seok Kim, Kyu Jeung Ahn, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 1998;22(4):450-456. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The b3 adrenergic receptor (b3-AR), expressed mainly in visceral fat of human, is involved in regulation of lipolysis and thermogenesis. The missense mutation of b3-AR gene, resulting in the replacement of tryptophan by arginine at position 64 (Trp64Arg), is associated with decreased resting metabolic rate, weight gain and development of obesity. The purpose of this study was to investigate the frequency of the b3-AR gene polymorphism in obese Koreans. Subjects and METHODS: b3-AR genotype was determined in 87 healthy Koreans who visited SMC for the purpose of health checking from Dec/1996 to Feb/1997. Oral glucose tolerance test was performed with 75 g glucose. Lipid profiles, insulin, C-peptide were measured. Anthropometric data was obtained from physical examination and medical records. The subjects with previously diagnosed diabetes mellitus, other endocrine diseases or chronic illness were excluded. To determine the polymorphism, genomic DNA was isolated and PCR and RFLP by MvaI were carried. RESULTS: 1. The difference in frequency of Trp64Arg mutation between two groups was highly significant. (12 subjects (63%) in obese group and 21 subjects (30%) in non obese group, p<0.02) 2. There was significantly high allele frequency in obese group. (obese group: 32 %; non obese group: 15 %, p<0.02). 3. According to BMI, there were significantly high WHR (0.88+0.04 vs 0.83+0.06,p=0.01), total body fat (29.8+7.4 vs 24.4+6.5%, p=0.01) and systolic blood pressure(132+19 vs 124+14mmHg, p=0.04) in obese group. 4. According to b3-AR genotype, there were significantly high WHR (0.830.056 vs. 0.860.05) and 120 min (260.5+171. 5 vs 355.9+234.6 pmol/L, p=0.04) insulin level during OGTT in heterozygote group. CONCLUSION: These results suggest that the frequency of the b3-AR gene mutation was significantly higher in obese Koreans and b3-AR gene polymorphism might play a role in the pathogenesis of obesity.

Insulin Gene Polymorphisms in non-insulin-dependent Diabetes Mellitus ( NIDDM ) in Korean.: Jin Suk Kwon, Seok Won Park, Bong Soo Cha, Young Duk Song, Churl Woo Ahn, Keun Soo Jang, Soo Jin Kim, Seung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(4):442-449. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Many epidemiologic and family studies indicated stronger influence of genetic factors in NiDDM compared to IDDM, and there has been investigations to identify the susceptibility genes but without definite results. Insulin gene with its regulator region has been considered as a possible candidate gene of NIDDM because of relative deficiency in insulin secretion. So, we investigated the possible relationship between insulin gene polymorphisms and NIDDM in Korean. METHODS: we investigated -23 Hph I and +1,127 Pst I restriction site on insulin gene region in 67 NIDDM patients and 33 healthy controls by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method, and compared the allelic frequencies. We also compared the insulin secretory capacity, degree of blood glucose control, and family history of diabetes mellitus according to insulin gene polymorphism. RESULTS: l. Insulin gene polymorphism on -23 Hph I restriction site or +1,127 Pst I restrietion site does not confer susceptibility to NIDDM in Korea, 2. No differences were observed in onset age, family history of diabetes mellitus, insulin secretory capacity, and degree of blood glucose control, according to insulin gene polymorphism. CONCLUSION: Insulin gene polymorphism on Hph I site and Pst I site probably does not play an important role in the pathogenesis of NIDDM in Korean population.

Angiotensin 1 Converting Enzyme ( ACE ) Gene Polymorphism According to Micro- and Mocro - angiopathy in non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Hyun Chul Lee, Ji Hyun Lee, Bong Soo Cha, Su Youn Nam, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1997;21(4):397-405. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Chronic micro- and macro-angiopathy in diabetes are clinically significant complications that affect both quality and length of life in diabetic patients. Angiotensin 1 converting enzyme (ACE) is of key importance in regulating systemic and renal circulation by converting angiotensin-1 into -2 and inactivating bradykinin, Recent reports suggest that the ACE gene polymorphism is associated with susceptibility to micro- and macro-angiopathy in diabetes. But the results are diffetent according to the type of diabetes and complication. METHODS: We investigated the alleles of the ACE gene and measured the ACE activity in the 169 cases of non-insulin dependent diabetic patients and in the 95 cases of controls matched with age and BMI. RESULTS: The measured ACE activity was well correlated with the count of D allele. We found no differences of ACE alleles between in diabetes and control. No association was found between ACE gene polymorphism and diabetic microangiopathy(retinopathy or nephropathy). But DD genotypes (homozy-gotes for the deletion polymorphism) and D allele were found more frequently in diabetic patients with coronary artery obstructive diseases than in patients without coronary artery obstructive diseases in coronary angiography. CONCLUSION: These data indicate that ACE gene polymorphism in non-insulin dependent diabetes is associated with coronary artery obstructive diseases, but not with chronic microangiopathy.

Relationship between Angiotensin I Converting Enzyme Gene Polymorphism and Vascular complications in Non-Insulin Dependent Diabetic Patients.: Byoung Gue Na, Tae Geun Oh, Sang Moo Jung, Sang Woo Oh, Jae Hong Choi, Ji Hyun Lee, Seong Su Koong, Seung Taik Kim; Korean Diabetes J. 1997;21(2):138-146. Published online January 1, 2001

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Abstract PDF: No abstract available.

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