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8 "Hyoung Doo Shin"
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Original Article
Polymorphisms of the Reg1α Gene and Early Onset Type 2 Diabetes in the Korean Population
Bo Kyung Koo, Young Min Cho, Kuchan Kimm, Jong-Young Lee, Bermseok Oh, Byung Lae Park, Hyun Sub Cheong, Hyoung Doo Shin, Kyung Soo Ko, Sang Gyu Park, Hong Kyu Lee, Kyong Soo Park
Korean Diabetes J. 2010;34(4):229-236.   Published online August 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.4.229
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  • 2 Crossref
AbstractAbstract PDFPubReader   
Background

The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.

Methods

We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.

Results

No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).

Conclusion

Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.

Citations

Citations to this article as recorded by  
  • A Novel Variant Of Regenerating Iα Gene (REG) In Type II Diabetics Among Pakistani Targeted Population
    Sadaf Saleem, Saeeda Baig, Sadia Farrukh, Mazhar Shafiq
    Journal of Rawalpindi Medical College.2023;[Epub]     CrossRef
  • Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus
    Eun Yeong Choe, Yong-ho Lee, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee
    Diabetes & Metabolism Journal.2012; 36(3): 230.     CrossRef
Retraction of Publication
Retraction: Polymorphisms of Kir6.2 Gene are Associated with Type 2 Diabetes and Blood Pressure in the Korean Population.
Bo Kyeong Koo, Hong Il Kim, Eu Jin Lee, Young Min Cho, Hyoung Doo Shin, Hak Chul Jang, Hong Kyu Lee, Kyong Soo Park
Korean Diabetes J. 2007;31(2):185-185.   Published online March 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.2.185
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  • 19 Download
PDF
Original Articles
Association between Genetic Polymorphisms in Hepatocyte Nuclear Factor 4alpha and Type 2 Diabetes in Koreans.
Eun Jung Lee, Soo Heon Kwak, Sun Wook Jo, Hyung Jin Choi, Hyoung Doo Shin, Min Kyong Moon, Young Min Cho, Hak Chul Jang, Kyong Soo Park, Houng Kyu Lee
Korean Diabetes J. 2006;30(1):10-16.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.10
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AbstractAbstract PDF
BACKGROUND
Hepatocyte nuclear factor-4alpha (HNF-4alpha) is a member of transcription factor network which is essential for the development and function of the beta cell. Furthermore mutations in the HNF-4alpha gene have been known to cause maturity-onset diabetes of the young. Therefore we aimed to examine the association between polymorphisms in the HNF-4alpha gene and the risk of type 2 diabetes (T2DM) and its related phenotypes in the Korean population. METHODS: Two single nucleotide polymorphisms (SNPs) in the HNF-4alpha gene, g.4681C>T and HNF-4alpha g.12352C>T (Thr139Ile), were genotyped in unrelated T2DM (n=760) and non-diabetic subjects (n=303). The genetic associations between these SNPs and the risk of T2DM and metabolic phenotypes were analyzed. RESULTS: There was no significant association between genetic polymorphisms in the HNF-4alpha and the risk of T2DM. However HNF-4alpha g.4681C>T increased total cholesterol in the recessive model (P = 0.02) and showed marginal association with fasting plasma glucose (P = 0.049) in the additive model. CONCLUSION: There was no significant association between genetic polymorphisms and the risk of T2DM in the Korean populations. But HNF-4alpha g.4681C>T was associated with higher level of total cholesterol and fasting plasma glucose.
Polymorphisms of Kir6.2 Gene are Associated with Type 2 Diabetes and Blood Pressure in the Korean Population.
Bo Kyeong Koo, Hong Il Kim, Eu Jin Lee, Young Min Cho, Hyoung Doo Shin, Hak Chul Jang, Hong Kyu Lee, Kyong Soo Park
Korean Diabetes J. 2005;29(5):440-450.   Published online September 1, 2005
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AbstractAbstract PDF
BACKGOUND: ATP-sensitive potassium channels are a heterooctamer of SUR1 and Kir6.2, which are key components in the insulin secretory mechanism. Whether common variants in the Kir6.2 gene are associated with type 2 diabetes and/or its associated phenotypes was investigated. METHODS: The Kir6.2 gene was sequenced in 24Korean DNA samples to identify common polymorphisms (frequency > 0.05). The common variants found among these samples were genotyped in a larger population including type 2 diabetic patients and nondiabetic subjects. RESULTS: Thirteen single nucleotide polymorphisms and one insertion/deletion polymorphism were identified in the Kir6.2 gene, with six common variants(g.-1709A>T, g.-1525T>C, g.67G >A [E23K], g.570C>T [A190A], g.1009A>G [1337V], and g.1388C>T) genotyped in 761 type 2 diabetic patients and 675 nondiabetic subjects. Four individual polymorphisms(g.-1525T > C, g.67G>A, g.1009A>G and g.1388C>T) appeared to be associated with type 2 diabetes (age, sex and BMI-adjusted odds ratio[OR]=0.751[0.584-0.967] in the recessive model on g-1525T>C, 1.193 [1.020-1.394] in the additive model in g.67G>A, 1.195 [1.022-1.399] in the additive model on g.1009A>G, 0.835 [0.717-0.973] in the additive model in g.1388C >T). The haplotype "ATACGC" in the Kir6.2 gene, composed of rare allele in the g.67 and g.1009, was also associated with a higher prevalence of type 2 diabetes (age, sex, and BMI- adjusted OR = 1.256 [1.067-1.479], P for logistic regression = 0.006). In addition g.67G>A and g.1009A >G in the KCNJ11 were strongly associated with a high systolic blood pressure. CONCLUSION: Polymorphisms in the Kir6.2 gene are associated with type 2 diabetes and blood pressure in the Korean population.
Glutathion S-Transferase M1 Gene Polymorphism is Associated with Type 2 Diabetic Nephropathy.
Jae Hyeon Kim, Min Kyong Moon, Sang Wan Kim, Hyoung Doo Shin, Young Hwan Hwang, Curie Ahn, Hak Cheol Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
Korean Diabetes J. 2005;29(4):315-321.   Published online July 1, 2005
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AbstractAbstract PDF
BACKGROUND
Oxidative stress may be a determinant of the development of diabetic nephropathy. Glutathione S-transferases(GST) can work as an endogenous antioxidant to protect cells from oxidative stress. Homozygous deletion of the mu and theta subclasses of GST(GST-M1 and GST-T1), and Val105Ile polymorphism of the pi subclass of GST(GST-P1) are associated with antioxidant enzyme activity. In this study, whether the Val105Ile of GST-P1, null genotype of GST-M1 and GST-T1 are associated with type 2 diabetic nephropathy were examined. METHODS: These GST subclasses were genotyped in 361 type 2 diabetic patients with retinopathy; the subjects were divided into two groups, those with an end stage renal disease(ESRD)(the case group n=177) and those(the control group, n=184) showing no signs of renal involvement. RESULTS: The frequencies of the GST-P1 Ile105Val and GST-T1 null genotypes were no different between the cases and controls. However, the frequency of the GST-M1 null genotype was significantly higher in the cases than the controls(61.7% vs. 51.1%, chi-square=4.09, P=0.043), which was still significant after correction for age, sex and duration of diabetes (P= 0.044). In addition, the GST-M1 null genotype showed an increased frequency between the controls and the cases with long and short durations of type 2 diabetes until the onset of ESRD(51.1, 58.9 and 65.5%, respectively; chi-square for trend=5.12, P=0.024). CONCLUSION: This is the first study to suggest that the GST-M1 gene polymorphism might contribute to the development of ESRD in type 2 diabetic patients.
Common Genetic Polymorphisms in the Promoter of Resistin Gene are Major Determinants of Plasma Resistin Concentrations in Humans.
Young Min Cho, Byung Soo Youn, Sung Soo Chung, Ki Woo Kim, Bo Kyeong Koo, Kang Yeol Yu, Hong Je Park, Hyoung Doo Shin, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
Korean Diabetes J. 2004;28(1):9-19.   Published online February 1, 2004
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AbstractAbstract PDF
BACKGROUND
Resistin has been postulated to be an important link between obesity and insulin resistance. Genetic polymorphisms in the resistin gene promotor have been suggested as a determinant of the expression of resistin mRNA, which is possibly associated with obesity and insulin resistance. In this study, the association between the genotype of the resistin promoter, and its plasma concentrations, were investigated. METHODS: The g.-537A>C and g.-420C>G polymorphisms in the resistin promoter were examined, and the levels of plasma resistin measured in the Korean subjects, both with and without type 2 diabetes. Haplotype-based promoter activity and the gel electrophoretic mobility-shift assays(EMSA) were also performed. RESULTS: The -420G and the -537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with the A-G(-537 A and -420G) haplotypes showed significantly higher plasma resistin levels than those that did not. The haplotypes A-G had modestly increased promoter activities compared to the other haplotypes. The EMSA revealed the -420 G allele to be specific for binding of the nuclear proteins from adipocytes and monocytes. However, neither polymorphism was associated with type 2 diabetes or obesity in our study subjects. CONCLUSION: Polymorphisms in the promoter of the resistin gene are major determinants of plasma resistin concentrations in humans
Genetic Association of Adiponectin Polymorphisms with Risk of Type 2 Diabetes Mellitus.
Yun Yong Lee, Nam Seok Lee, Young Min Cho, Min Kyong Moon, Hye Seung Jung, Young Joo Park, Hong Je Park, Byoung Soo Youn, Hong Kyu Lee, Kyong Soo Park, Hyoung Doo Shin
Korean Diabetes J. 2003;27(6):438-448.   Published online December 1, 2003
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BACKGROUND
Adiponectin, an adipocyte-secreted protein, is known to modulate insulin sensitivity, glucose homeostasis and the development of atherosclerosis. Recently, several single nucleotide polymorphisms (SNPs) in the adiponectin gene have been reported to be associated with type 2 diabetes and components of the insulin resistance syndrome. METHODS: The frequencies of SNP T45G and G276T of the adiponectin gene was examined in 493 unrelated type 2 diabetic and 136 non-diabetic control Korean subjects. The clinical characteristics and plasma adiponectin levels of the subjects were compared within these genotypes. RESULTS: The T allele at SNP45 was significantly more frequent in the type 2 diabetes than in the control subjects (71.6 vs. 64.3%, p=0.013). The subjects with the G/G genotype of SNP45 were at reduced risk for type 2 diabetes (OR: 0.495, 95% CI 0.246-0.995, p=0.048) compared with those having the T/T genotype. However, there were no statistically significant differences in allele the frequencies (G frequency in the control vs. the diabetic group 73.9 vs. 68.9%, p=0.106) and genotype frequencies at SNP276 between groups. The subjects with the T/T genotype at SNP45 had higher a body mass index (24.6+/- 3.1 vs. 24.1+/-2.8 kg/m2, p=0.036) and serum triglyceride levels (2.03+/-1.31 vs. 1.87+/-1.38 mmol/1, p=0.041) than the T/G+G/G genotypes in the diabetic group. Those with the T/T genotype also had lower plasma adiponectin levels than those without T/T genotype at SNP45 in the control group (6.11+/-3.10 vs. 8.24+/-4.24 g/mL, p=0.043). There was a similar trend in diabetic group, but this did not reach statistical significance (4.32+/-2.81 vs. 4.96+/-3.26 g/mL, p=0.097). The SNP276 had no association with the clinical features of insulin resistance or plasma adiponectin level. CONCLUSION: The T/T genotype of SNP45 in the adiponectin gene was associated with a low adiponectin level, high body mass index, the serum triglyceride level and risk of type 2 diabetes mellitus. The SNP276 in the adiponectin gene may not be an important determinant of insulin resistance or type 2 diabetes in Korean subjects.
Association between Type 2 Diabetes and Genetic Variations in Uncoupling Protein 2, beta3-Adrenergic Receptor, and Peroxisome Proliferator-Activated Receptor gamma in Korean.
Min Kyong Moon, Young Min Cho, Hye Seung Jung, Tae Yong Kim, Yun Yong Lee, Joong Yeol Park, Ki Up Lee, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Hyoung Doo Shin
Korean Diabetes J. 2002;26(6):469-480.   Published online December 1, 2002
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AbstractAbstract PDF
BACKGROUND
Type 2 diabetes mellitus is a multifactorial disease influenced by numerous genetic and environmental factors. The uncoupling proteins, 2 (UCP2), beta3-adrenergic receptor ADRB3, and peroxisome proliferator-activated receptor gamma PPAR gamma, are genes involved in energy expenditure and fatty acid metabolisms, ans are therefore regarded as candidate genes for type 2 diabetes. In this study, we examined whether the known polymorphisms of UCP2, ADRB3 and PPAR gamma are associated with type 2 diabetes in the Korean population. METHODS: We studied 516 type 2 diabetic patients and 147 control subjects. The enrollment criteria for the control subjects were as follows; age > 60 years, no family history of diabetes in their first-degree relatives, a fasting plasma glucose (FPG) < 6.1 mmol/L, and a HbA1C < 5.8%. Height, weight, waist and hip circumference, FPG, 2 hour-plasma glucose after 75g-glucose load (2h-PG), blood pressure, lipid profile, and fasting insulin level were measured. The Ala55Val polymorphism of the UCP2, Trp64Arg polymorphism of the ADRB3, and Pro12Ala polymorphism of the PPAR gamma were determined by single base extension method. RESULTS: The allele frequency of the Ala55Val variant of the UCP2 tended to be higher in the control subjects than in the type 2 diabetic patients (0.497 vs. 0.456, p=0.064). The allele frequencies of the Trp64Arg polymorphism of the ADRB3, and the Pro12Ala polymorphism of the PPAR gamma, were comparable between the diabetic patients and the control subjects (0.141 vs. 0.152 and 0.033 vs. 0.041, respectively). In the control subjects, the Ala55Val polymorphism of the UCP2 was associated with a significantly lower 2h-PG compared to the wild type (6.0 +/- 0.8 mmol/L vs. 6.6 +/- 0.7 mmol/L, p=0.002). The female control subjects, with the ADRB3 Trp64Arg variant, had a significantly lower triglyceride level than those without the variant (1.36 +/- 0.53 mmol/L vs. 1.74 +/- 0.82 mmol/L, p=0.020). The type 2 diabetic patients, with the ADRB3 Trp64Arg variant showed a significantly lower body mass index (23.6 +/- 2.6 kg/m2vs. 24.6 +/- 3.0 kg/m2, p=0.001). The PPAR gamma Pro12Ala variant, was not associated with any of the features of insulin resistance. The combined genotype of the Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma was less frequent among the type 2 diabetes patients than the control subjects (0.020 vs. 0.056, p=0.039). CONCLUSION: The Ala55Val variant of the UCP2, the Trp64Arg variant of the ADRB3 and the Pro12Ala variant of the PPAR gamma, were not associated with type 2 diabetes in the Korean population. However, the Ala55Val variant of the UCP2 was associated with a lower 2h-PG in the control subjects and the Trp64Arg variant of the ADRB3 was associated with a lower triglyceride level in the female control subjects. Further study may be required to elucidate if the combined genotype of Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma would be protective against type 2 diabetes.

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