Biomedical subjects

Kyong Soo Park

Publications and source records attributed to Kyong Soo Park.

At least 19 recordsLinked to original sources

PubMed2026

Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus.

BACKGRUOUND: High 1-hour plasma glucose (1-h PG) level has been proposed by the International Diabetes Federation to identify high-risk individuals and diagnose type 2 diabetes mellitus (T2DM). In a longitudinal cohort, we examined T2DM risk, β-cell function, and the effects of genetic and lifestyle factors on high 1-h PG. METHODS: We analyzed 7,464 participants without T2D at baseline from a community-based prospective cohort in Korea, who underwent biennial 2-h 75-g oral glucose tolerance tests over 14 years. Incident T2D risk were assessed across 1-h PG groups: < 155, 155-208, and ≥ 209 mg/dL. In 6,588 participants with at least two 1-h PG measurements, we analyzed 1-h PG trajectories by T2D polygenic risk score (PRS; low, 1st quintile; intermediate, 2nd-4th quintiles; high, 5th quintile) and lifestyle, assessed using Life's Essential 8. RESULTS: Compared to the <155 mg/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; P<0.001) for 155-208 mg/dL, and 6.81 (95% CI, 5.81 to 7.98; P<0.001) for ≥209 mg/dL. Both groups had lower baseline disposition index compared to the <155 mg/dL group (57.3% and 72.7%, respectively; both P<0.001). Higher T2DM PRS was associated with elevated baseline 1-h PG (low: 131 mg/dL, intermediate: 141 mg/dL, high: 151 mg/dL) and faster increase in 1-h PG (1.36 vs. 1.85 vs. 2.21 mg/dL/year; all P<0.001). Importantly, healthy lifestyle attenuated the rate of increase across all PRS groups. CONCLUSION: High 1-h PG predicts T2DM risk and is associated with β-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.

Humans↗

PubMed2007

Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs.

BACKGROUND: Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation. RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.

Aging↗

PubMed2006

Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month prospective study.

Adiponectin and resistin are proteins that affect insulin resistance and atherosclerosis significantly. We investigated adiponectin and resistin concentrations as predictors of cardiovascular events in Korean patients with type 2 diabetes. The study in 2001 comprised 343 unrelated patients with type 2 diabetes (65+/-9.2 years old). They were followed up for 42 months. The baseline duration of diabetes, smoking status and history of cardiovascular diseases (CVD) were recorded. BMI, blood pressures, HbA1c, lipid profiles, ECG, creatinine and urine microalbumin were measured. Adiponectin and resistin were measured using enzyme-linked immunosorbent assays. The primary endpoint was defined as one of cardiovascular death, myocardial infarct, CABG, stroke, unstable angina or overt nephropathy. Thirty-eight patients (11.1%) experienced primary endpoint during the follow-up. After adjustment for age, sex, BMI, blood pressure and lipid status, participants in the lowest quartile of adiponectin levels compared with the highest had significantly increased risk of primary endpoint (relative risk=3.03; 95% CI 1.09-8.41; p=0.034). In contrast, resistin level had no influence on the risk of primary endpoint. A low level of adiponectin, not resistin, was a significant risk factor for the development of cardiovascular events in these Korean patients with type 2 diabetes.

Adiponectin↗

PubMed2006

Acylated ghrelin secretion is acutely suppressed by oral glucose load or insulin-induced hypoglycemia independently of basal growth hormone secretion in humans.

BACKGROUND: Ghrelin has been reported to be the natural ligand of growth hormone (GH) secretagogue receptor, and it is known that exogenous ghrelin administration strongly stimulates GH release in humans. However, the effects of endogenous ghrelin on GH secretion and changes in ghrelin levels during dynamic changes in GH levels are not well understood. METHODS: Therefore, we measured circulating acylated ghrelin concentrations during oral glucose tolerance tests (OGTTs) in patients with active acromegaly (AA, n = 9) and in age/sex/BMI-matched group A controls (n = 12), and during insulin tolerance testing (ITT) in patients with GH deficiency (GHD, n = 10) and in group B controls (n = 10). Plasma acylated ghrelin, serum GH, insulin and glucose levels were measured during each test. RESULTS: Fasting plasma ghrelin levels correlated negatively with serum insulin levels in both group A and B controls (r = -0.665; p < 0.05) but not in patients with AA or GHD. During OGTTs, circulating ghrelin levels decreased significantly with a nadir at 30 min in both patients with AA (p < 0.05) and group A controls (p < 0.01). Also, ITTs were followed by a significant decrease in circulating ghrelin levels with a nadir at 30 min in patients with GHD (p < 0.05) and in group B controls (p < 0.05). CONCLUSION: The results of the study show that at baseline acylated ghrelin levels do not differ with respect to the GH status (GH excess or GH deficiency) and, furthermore, the suppression of acylated ghrelin levels during OGTT or ITT is independent of the GH response to the tests.

Acromegaly↗

PubMed2006

Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.

CONTEXT: Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. OBJECTIVE: The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. DESIGN AND PATIENTS: The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. RESULTS: Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). CONCLUSION: The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.

Aged↗

PubMed2006

Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells.

Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial DNA content were increased with differentiation, which was accompanied by the increase of the amount of ATP (4-fold) and its by-product reactive oxygen species (2.5-fold). The expression of various antioxidant enzymes including mitochondrial and cytoplasmic superoxide dismutases, catalase, and peroxiredoxins showed a dramatic change during the early differentiation. In conclusion, HESC differentiation was followed by dynamic changes in mitochondrial mass, ATP and ROS production, and antioxidant enzyme expressions. Therefore, the HESCs would serve as a good model to examine the mitochondrial biology during the early human differentiation.

Adenosine Triphosphate↗

PubMed2006

Rapidly increasing diabetes-related mortality with socio-environmental changes in South Korea during the last two decades.

Diabetes mellitus is the result of complex interactions involving many genes and environmental factors, and rapid socio-environmental changes have been strongly associated with the development of diabetes. In this study, we examined the trends in diabetes mortality and associated socio-environmental changes that have occurred in South Korea over the last 20 years. Data from a national database and government reports for the years from 1983 to 2001 were analyzed. The data included mortality, socio-economic changes, physical activity and dietary pattern indicators. Deaths from diabetes per 100,000 people increased from 5.3 in 1983 to 18.4 in 2001. Along with increasing diabetes-related mortality, many socio-economic indices (gross domestic production, proportion of tertiary industry and urbanization rate), proxies for physical activity (numbers of cars and time spent watching television) and diet indices (animal protein intake and fat intake) showed remarkable changes. To counter increasing prevalence of diabetes and its related mortality in South Korea, multidirectional efforts including lifestyle modification should be mandatory features of future public health policy.

Aging↗

PubMed2006

PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats.

OBJECTIVE: There is still debate as to whether antiatherosclerotic effect of PPARgamma ligands is dependant on PPARgamma gene itself or some other pathway. METHODS AND RESULTS: To investigate the effect of PPARgamma gene modulation on neointima formation after balloon injury, we delivered adenoviral vectors expressing the wild-type (WT) dominant negative (DN) PPARgamma, or a control gene (beta-galactosidase [BG]) into carotid artery after balloon injury in rosiglitazone (a PPARgamma ligand)-treated (R+) (3 mg/kg/d) and nontreated (R-) rats. Two weeks after gene delivery, in both R+ and R- animals, the PPARgamma-WT gene transfer showed a significantly lower intima-media ratio (IMR) than control group. Moreover, the delivery of a PPARgamma-DN form showed the highest IMR (in R+WT, 0.51+/-0.15; R+BG, 0.89+/-0.14; R+DN, 1.20+/-0.18, P<0.05 and in R-WT, 0.91+/-0.21; R-BG, 1.44+/-0.23; R-DN, 1.74+/-0.29, P<0.05). Proliferation and migration showed same result pattern as IMR. In addition, apoptotic indices were significantly higher in the PPARgamma-WT gene transferred group than in the PPARgamma-DN group. CONCLUSIONS: In vivo transfer of the PPARgamma-WT gene was found to inhibit smooth muscle proliferation, sustain apoptosis, and reduce neointima formation after balloon injury irrespective of rosiglitazone treatment. These results indicate that PPARgamma overexpression itself has a protective role against restenosis after balloon injury.

Animals↗

PubMed2006

Proteomic analysis of cellular change involved in mitochondria-to-nucleus communication in L6 GLUT4myc myocytes.

Genetic or biochemical abnormalities in mitochondria are closely associated with apoptosis, aging, cancer, and other chronic degenerative diseases. Mitochondrial dysfunction resulting from mitochondrial DNA (mtDNA) depletion dispatches retrograde signals to the nucleus to compensate by altering the expression of various genes. In this study, a proteomic approach was used to gain insight into the nuclear gene targets of mitochondrial stress signaling and the pathophysiological mechanisms associated with mitochondrial dysfunction. We have used 2-DE to characterize the nuclear gene responses resulting from mtDNA depletion in L6 GLUT4myc myocytes. Our results showed that 77 polypeptides were differentially expressed in mtDNA-depleted cells; 33 polypeptides were down-regulated and 44 polypeptides were up-regulated. Of these differentially expressed polypeptides, 40 were identified as 36 different proteins by MALDI-TOF MS. These proteins are related to various cellular responses, such as apoptosis, cellular metabolism, signaling and cytoskeleton functions. It is suggested that the insulin resistance developed in mtDNA-depleted myocytes may be associated with disorganization of cytoskeleton assembly, and that cellular mtDNA depletion might promote the ability to evade apoptosis or other death effectors.

Animals↗

PubMed2006

Differential expression of vitreous proteins in proliferative diabetic retinopathy.

PURPOSE: To identify vitreous proteins that were differentially expressed in patients suffering from proliferative diabetic retinopathy with active neovascularization. METHODS: The vitreous samples of 15 active proliferative diabetic retinopathy patients were analyzed by two-dimensional gel electrophoresis and mass spectrometry, and the results were compared with those from age-matched patients with macular hole. RESULTS: Twenty-five protein spots were identified in the two-dimensional gel electrophoresis gels. Eight proteins (pigmented epithelium derived factor, serine protease inhibitor, apolipoprotein A-IV precursor, prostaglandin-H2 D-isomerase, a(1)-antitrypsin precursor, ankyrin repeat domain 15 protein, alpha2-HS-glycoprotein, and beta V spectrin) in the 25 spots were expressed significantly differently between the macular hole and proliferative diabetic retinopathy patients (p value < 0.05). Five proteins were upregulated in the proliferative diabetic retinopathy patients, and three were downregulated (p value < 0.05). CONCLUSIONS: We constructed vitreous protein profiles for proliferative diabetic retinopathy patients and identified eight candidate proteins believed to be involved in the pathogenesis of proliferative diabetic retinopathy.

Aged↗

PubMed2006

Synthesis and PPAR-gamma ligand-binding activity of the new series of 2'-hydroxychalcone and thiazolidinedione derivatives.

Fifteen chalcones and three thiazolidinedione (TZD) chalcones were prepared to evaluate their peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activities. Among the three TZDs, one compound possessed PPAR-gamma transactivation potential, while the others showed antagonistic activity against PPAR-gamma transactivation. Among the chalcones, compound 5 was the most potent, and structure-activity relationship studies indicated that a methoxyl group in position C-4 and hydroxyl group in position C-4' or 5' in chalcone plays a key role in determining the potency of PPAR-gamma activation.

Chalcone↗

PubMed2006

Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes.

OBJECTIVE: The dysregulation of adipokines is closely associated with the pathogenesis of insulin resistance and type 2 diabetes. Retinol-binding protein-4 (RBP4), a new adipokine, was recently reported to provide a link between obesity and insulin resistance. Here, we examined the relation between plasma RBP4 concentrations and various metabolic parameters in humans. RESEARCH DESIGN AND METHODS: An enzyme-linked immunosorbent assay was developed to measure human RBP4 plasma concentrations, which were then compared with various parameters related to insulin resistance in subjects with normal glucose tolerance (NGT; n = 57), impaired glucose tolerance (IGT; n = 48), and type 2 diabetes (n = 49). RESULTS: Plasma RBP4 concentrations were higher in the IGT and type 2 diabetic groups than in the NGT group (median 18.9 [range 11.2-45.8], 20.9 [9.9-48.5], and 18.1 microg/ml [9.3-30.5], respectively). However, no difference was found between plasma RBP4 concentrations in the IGT and type 2 diabetic groups. Plasma RBP4 concentrations were found to be associated with sex, waist circumference, fasting plasma glucose, and insulin resistance. Of these, sex and fasting plasma glucose levels were found to be independent determinants of plasma RBP4 concentration. CONCLUSIONS: Plasma RBP4 concentrations were found to be elevated in subjects with IGT or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance.

Adult↗

PubMed2006

SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy.

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). Genetic susceptibility plays an important role in the development and progression of diabetic nephropathy. Previous studies have revealed that polymorphisms in the SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) gene, which encodes solute carrier family 12 member 3, might contribute to genetic susceptibility to diabetic nephropathy and essential hypertension. In this study, we examined whether the SLC12A3 gene locus is associated with ESRD resulting from diabetic nephropathy. We genotyped 11 common single nucleotide polymorphisms (SNPs) in the SLC12A3 gene in 177 patients with ESRD due to type 2 diabetes and 184 patients with diabetic retinopathy but with no signs of renal involvement. Three SNPs (g.34372G>A [Arg913Gln], g.39143G>A, and g.41727C>T) were found to be associated with ESRD due to diabetic nephropathy. These three SNPs were in complete linkage disequilibrium. Haplotype 4 in block 2 (18806C, 21822C, 34372A, 39143A, 39240T, 39375C, and 41727T) showed a significant association with ESRD due to type 2 diabetes (P = 0.0028). These results suggest that the SLC12A3 gene locus is associated with ESRD due to diabetic nephropathy.

Adult↗

PubMed2005

Polymorphisms in the leptin receptor (LEPR)--putative association with obesity and T2DM.

Leptin plays an important role in regulating adipose-tissue mass. Leptin controls energy balance and food intake through the leptin receptor in the hypothalamus of the brain, which suggests that some polymorphisms of the leptin receptor gene (LEPR) might contribute to obesity or obesity-related diseases. In an effort to identify genetic polymorphisms in a potential candidate gene for obesity and type 2 diabetes mellitus (T2DM) in the Korean population, we have sequenced the LEPR gene. Thirty-five sequence variants were identified (including 9 novel polymorphisms): 1 single nucleotide polymorphism (SNP) in the promoter region, 1 SNP in the 5' UTR, 8 SNPs in exons (3 non-synonymous SNPs), 23 SNPs in introns, 1 ins/del in the 3' UTR, and 1 SNP in the 3' downstream region. To investigate possible association of LEPR polymorphisms with body mass index (BMI) and the risk of T2DM, we genotyped for 11 polymorphisms in the Korean population (n = 1,463). Using statistical analyses, no significant associations between the genetic polymorphisms in the LEPR gene and the risk of T2DM were detected. However, one non-synonymous SNP in exon 3, +5193G > A (Arg109Lys), showed marginal association with BMI (P = 0.02) and gene dose-dependent genetic effects were observed. The present study provides information about additional genetic polymorphisms in LEPR and positive associations of those polymorphisms with BMI in the Korean population.

Aged↗

PubMed2005

Resistin is secreted from macrophages in atheromas and promotes atherosclerosis.

OBJECTIVE: Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human. METHODS AND RESULTS: Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytes/macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10-100 ng/mL for 4 approximately 24 h). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3-2.5 (p<0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p<0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration. CONCLUSIONS: Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans.

Actins↗

PubMed2005

Genetic polymorphisms in the transforming growth factor beta-induced gene associated with BMI.

In an effort to identify genetic polymorphisms in potential candidate genes for type 2 diabetes mellitus (T2DM), we have sequenced the transforming growth factor beta-induced gene (TGFBI), and examined the association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 normal controls). Twenty-eight polymorphisms were identified in TGFBI. Although no significant associations were detected with the risk of T2DM, one SNP in intron 16 (c.2011+137C>T) and one SNP in the 3' untranslated region (UTR) (c.2589T>G), showed significant association with the levels of insulin and body mass index (BMI) among nondiabetic controls. The lower insulin and BMI were observed in individuals who carry one or two copies of minor alleles than others. For example, the highest BMI (24.21 kg/m(2)) in individuals with homozygote major alleles (T) of c.2589T>G (n=99), the intermediate BMI (23.68 kg/m(2)) in individuals with heterozygote alleles (n=156), and the lowest BMI (22.69 kg/m(2)) in individuals with homozygote minor alleles (G) (n=57, P=0.005) were observed. The present study provides, for the first time, information about genetic polymorphisms in TGFBI and positive associations of those polymorphisms with levels of insulin and BMI in the Korean population.

3' Untranslated Regions↗

PubMed2005

Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells.

Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates the release of growth hormone at the hypothalamus and pituitary level. Although GHS-Rs are expressed in a variety of peripheral tissues, little is known about its effect on bone independent of GH/IGF-1 axis. This study was undertaken to investigate whether ghrelin exerts a direct effect on osteoblasts. We identified mRNA and protein expression of GHS-R in primary osteoblasts as well as a number of osteoblastic cell lines, including MC3T3-E1, ROS 17/2.8, UMR-106, MG63, and SaOS2 cells. Treatment of ghrelin (10(-11) to 10(-7) M) to MC3T3-E1 cells showed dose-dependent stimulation of proliferation, which was abrogated by treatment with [d-Lys]-GHRP-6 (10(-3) M), a selective antagonist of the ghrelin receptor. Ghrelin activated ERK1/2 MAPK and pretreatment with MAPK kinase inhibitors, PD98059 attenuated the ghrelin-induced cell proliferation. Ghrelin also inhibited TNFalpha-induced apoptosis and suppressed caspase-3 activation that occurs in response to TNFalpha as well as during in vitro differentiation process. Moreover, ghrelin treatment enhanced in vitro osteoblast differentiation as evidenced by matrix mineralization, alkaline phosphatase activity, and osteoblast-specific gene expression. These results suggest that ghrelin promotes proliferation and differentiation and inhibits apoptosis of osteoblasts.

Animals↗

PubMed2005

Association of HLA-DR and -DQ genes with Graves disease in Koreans.

Graves disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and DQA1*0501 in Caucasians. However, the association of HLA with GD is less clear-cut in East Asian populations. We analyzed HLA-DRB1 and -DQB1 associations with GD in 198 Korean patients compared with 200 healthy controls. HLA-DRB1*0803 (27.8% vs. 14.5% in controls, OR = 2.27, corrected p [p(c)] = 0.03) and *1602 (5.1% vs. 0%, OR = 22.34, p(c) = 0.03) alleles and closely linked haplotypes, DRB1*0803-DQB1*0601 and DRB1*1602-DQB1*0502, conferred susceptibility to GD in Koreans. Weak association of DRB1*0301 with GD susceptibility was observed in male patients only (12.5% vs. 3.5%, OR = 3.57, p < 0.05). HLA-DRB1*0101, *0701, *1202, and *1302 alleles were weakly associated with resistance to the disease (OR < 0.5, p < 0.05). Some HLA alleles were weakly associated with clinical characteristics in GD patients. Patients with DRB1*1301-DQB1*0603 developed their diseases in younger ages and were more frequently associated with larger goiter (p < 0.05). Although HLA class II alleles associated with GD in Koreans were different from those in Caucasians, some associations are shared, such as association of DRB1*0301 in male patients and protective effect of DRB1*0701 to GD susceptibility.

Adolescent↗