Hee-Baeg Choi

Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-γ genes in the Korean population

Cytokines play a crucial role in regulating the immune and inflammatory responses. The collective influence of several cytokines can regulate immune responses as complex as those underlying allograft rejections or autoimmune diseases. Polymorphisms in the regulatory regions of the cytokine genes may influence their expression. Therefore, the polymorphisms of cytokine genes are potentially important as genetic predictors of the disease susceptibility or clinical outcome. In 311 unrelated healthy Korean individuals, we investigated the polymorphisms of cytokine genes (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, and interferon-gamma [IFN-gamma]), which had been previously reported to be associated with a number of immune diseases, transplant complications, and direct or indirect influences on the level of expression and production. And we also compared the results to those published for other populations. The genotype distributions were consistent with the assumption of the Hardy-Weinberg equilibrium, with the exceptions of IL-1B +3954 and IL-6-174 polymorphisms. The polymorphisms examined in this study were almost similar to that observed in Asian populations. There were significant differences of the polymorphisms, except for IL-4 receptor alpha +1902, between Korean and other populations. Comparing the alleles associated with higher level of expression and production, IL-1B +3954*T, IL-2-330*G, and IL-4-590*T alleles were significantly higher, and IL-1RN*A2, IL-10-1082*G, and IFN-gamma*2 alleles were lower in Koreans than other populations. Especially in IL-6 promoter -174 polymorphism, we found only the G allele associated with higher plasma IL-6 levels. In haplotype analysis of IL-10 promoter polymorphisms, the GCC haplotype, associated with higher expression of IL-10, was significantly lower in Koreans. These results may be helpful for understanding transplant-related complications, immune or autoimmune diseases, and malignant diseases in the Korean population.

Association of HLA Alleles with Autoimmune Thyroid Disease in Korean Children

Backgrounds: Data regarding genetics of Hashimoto’s disease (HD) and Graves’ disease (GD) in Korean children are lacking. Methods: 73 patients with autoimmune thyroid disease (AITD; HD 32, GD 41) were recruited. We analyzed human leukocyte antigen (HLA) class I and HLA-DRB1 by PCR-SSP, and compared them with those of 159 controls. Results: In AITD, the allele frequencies of HLA-A*02, -B*46, -Cw*01 and -DRB1*08 were higher and those of HLA-A*30, -B*07, -Cw*07 and -DRB1*01 were lower than in controls. In HD, those of HLA-B*46 and -Cw*01 were higher and those of HLA-DRB1*01 and -Cw*07 were lower than in controls. In GD, those of HLA-A*02, -B*46, -Cw*01 and -DRB1*08 were higher and those of HLA-DRB1*07 and -Cw*07 were lower than in controls. Between HD and GD, there were no significant differences in allele frequencies. The risk of AITD in the presence of both HLA-B*46 and -Cw*01 is higher than in the presence of either allele alone. Conclusion: The susceptible and protectable alleles in HD are similar to those in GD. Coexistence of HLA-B*46 and -Cw*01 may be a genetic gene marker for early-onset AITD in Koreans.

Distribution of seven polymorphic markers and haplotypes within the human TNF gene cluster in Koreans

We examined the distribution of polymorphic elements within the tumor necrosis factor (TNF) gene cluster in 133 normals and in 20 Korean families and compared our data with the results of Caucasians. The genotypes that are shown frequently are TNF a6 (33.8%), TNF b5 (46.6%), TNF c1 (79.3%), TNF d3 (34.6%), TNF e3 (86.5%), TNFB*2 (51.5%), and TNF(-308) A (91.4%). In comparison, TNFa 6 (33.8%), TNFa 13 (4.1%), TNFb 5 (46.6%), TNFd 1 (7.5%), TNFd 3 (34.6%), TNFe 3 (86.5%), TNFe 4 (6.8%), and TNF(-308) A (91.3%) were found more frequently in Koreans than Caucasians (p < 0.01). TNFa 14, TNFa 15, TNFd 8, and TNFe 4 alleles were found only in Korean controls. However, TNFb 6 and TNFb 7 alleles were not found in this study. From the TNF gene of TNFa, TNFb, TNFc, TNFn, TNF(-308), TNFd, and TNFe, 49 different TNF haplotypes were found in 20 Korean families. These data suggest that the TNF microsatellite haplotypes constitute a highly polymorphic system and that will provide useful information on the association between the TNF marker and the immune disease.

Association of MICA Alleles with Autoimmune Thyroid Disease in Korean Children

Background. Major histocompatibility complex class I chain-related gene A (MICA) is a ligand for the activating NKG2D receptor expressed on natural killer (NK) cells. We aimed to assess the association of MICA polymorphism with autoimmune thyroid disease (AITD) in Korean children. Methods. Eighty-one patients with AITD were recruited. We analyzed MICA polymorphisms by PCR-SSP and compared the results with those of 70 healthy controls. Results. In AITD, the allele frequencies of MICA∗010 (OR = 2.21; 95% CI, 1.30–3.76, P < 0.003, P c < 0.042) were higher than those of controls. Patients who did not have thyroid-associated ophthalmopathy showed higher frequencies of MICA∗010 (OR = 2.99; 95% CI, 1.47–6.08, P < 0.003, P c < 0.042) and lower frequencies of MICA∗008 (OR = 0.08; 95% CI, 0.01–0.62, P < 0.001, P c < 0.014) compared to those of controls. HLA-B∗46, which shows the strongest association with AITD compared with other HLA alleles, showed the strongest linkage disequilibrium with MICA∗010. Analyses of the associations between MICA∗010 and HLA-B∗46 with AITD suggest an association of the MICA allele with AITD. Conclusions. Our results suggest that innate immunity might contribute to the pathogenesis of AITD.

665Polymorphism of cytokines and killer immunoglobulin-like receptor (KIR) gene in children with Bacille Calmette-Guérin lymphadenitis

(KIR) gene in children with Bacille Calmette-Guérin lymphadenitis Hyo Jin Kwon, MD; Seong Joon Kim, MD; Jong-Hyun Kim, MD, PhD; HeeBaeg Choi; Tai-Gyu Kim, MD, PhD; Dae Kyun Koh, MD, PhD; Jin Han Kang, MD, PhD; Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea