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한국인 건선 환자에서의 IL-1B (-511, +3954)와 IL-1RN 유전자의 다양성 조사
김양겸,표철우,김태윤,김태규,Kim, Yang-Kyum,Pyo, Chul-Woo,Kim, Tae-Yoon,Kim, Tai-Gyu 대한면역학회 2003 Immune Network Vol.3 No.3
Background: Psoriasis is an inflammatory skin disorder that is characterized by a marked proliferation of keratinocytes, vascular dilation and leukocyte infiltration. Cytokines play important roles in the pathogenesis of inflammatory disorders. An overexpression of proinflammatory cytokines was characterized in psoriasis plaque. Among these cytokines, IL-$1{\beta}$ is major pro-inflammatory cytokine synthesized during the infection and inflammatory process. The IL-1 receptor antagonist (IL-1Ra) competes for the same IL-1 receptor for $IL-1{\alpha}$ and $-1{\beta}$, which prevents activation of the target cells. Three single nucleotide polymorphisms (SNPs) in the IL-$1{\beta}$ gene have been reported at position -31, -511 and +3954. Within the IL-1Ra gene (IL-1RN), there is a variable number of tandem repeats (VNTR) of an 86 bp length in intron 2. These polymorphisms related to cytokine production and associated with various diseases. Methods: We investigated the polymorphisms of IL-1B (promoter -511 and +3954) and IL-1RN on 114 psoriasis patients and 311 healthy normal controls in Korean. We performed PCR-RFLP on single nucleotide polymorphisms (SNPs) of IL-1B (promoter -511 and +3954) and fragment analysis on IL-1RN 86 bp VNTR polymorphism. Results: The frequency of IL-1B $-511^*1$ allele (patients vs. controls; 50.0% vs. 42.3%, RR=1.4) was significantly increased and IL-1B $-511^*2$ allele (patients vs. controls; 50.0% vs. 57.7%, RR=0.7) decreased in psoriasis patients compared to normal controls. We also analyzed the IL-1B -511 polymorphism according to patients' characters (age of onset, sex and family history). The IL-1B -511 alleles were significantly associated in patients with male and family history than health normal controls. There were no significant associations of IL-1B +3954 and IL-1RN polymorphisms with psoriasis patients. Conclusion: These results suggest that the polymorphism of IL-1B -511 could be genetic susceptibility to psoriasis in Koreans.
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HIV감염과 MICA (MHC class I chain-related A) 대립 유전자의 연관성
강문원,위성헌,김양리,이주실,표철우,한훈,김태규,Kang, Moon-Won,Wie, Seong-Heon,Kim, Yang-Ree,Lee, Joo-Shil,Pyo, Chul-Woo,Han, Hoon,Kim, Tai-Gyu 대한면역학회 2001 Immune Network Vol.1 No.2
Background: A large number of diseases occur in association with specific HLA-B or-C alleles. Recently a new gene, termed maj or histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown. However, it is structurally similar to HLA class I genes. MICA gene is polymorphic and is potentially associated with several diseases. Methods: To evaluate the association of MICA gene in Korean patients with human immunodeficiency virus 1 (HIV-1) infections, Polymerase chain reaction-Sequence specific primer (PCR-SSP) was done for MICA alleles in the extracellular exons, and a microsatellite analysis for GCT repeat polymorphisms in the TM exon was also completed. Results: In 199 Korean healthy controls, 7 alleles were observed and the frequencies for each allele were MICA008 (44.7%), MICA0 10 (34.2%), MICA002 (31.7%), MICA004 (23.6%), MICA0 12 (2 1.6%), MICA009 (19.6%), and MICA007 (6.5%). When 65 HIV seropositive patients were analyzed, MICA007 allele frequency was significantly higher than in controls (15.4% vs 6.5 %, RR=2.6, p<0.04). In contrast, the frequencies of other MICA alleles and microsatellite alleles in the transmembrane region of MICA gene were not significantly different between HIV seropositive patients and controls. The tight linkage between MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon was observed as follows; MICA002/A9, MICA004/A6, MICA007/A4, MICA008/A5.1, MICA0 10/A5, and MICA0 12/A4 in both groups. No significant difference between patients and controls was observed in the haplotype frequencies of MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon. Conclusion: The data suggest that immune functions related with MICA gene may affect a HIV infections.
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이혜정,김수연,박소양,표철우,한훈,양일호 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1
연구배경: HLA-class I 유전자는 높은 다양성을 가지고 있다. 장기이식 시 GVHD 유발에 많은 영향을 끼치는 것으로 알려져 있는 HLA-B locus는 258개의 대립유전자가 존재한다고 알려져 있으며 대부분 exon 2, 3 부위에 다형성을 갖는다. 방법: 대립유전자형을 구분하는 방법으로는 항원 항체반응을 이용한 혈청학적 방법이 주로 사용되어 왔으나 최근에는 분자생물학적인 방법들이 개발되어 이용되고 있다. 한국인에서는 HLA-B49, B50, B18, B45, B73 등이 존재하지 않는다고 알려져 있으나 DNA수준에서의 HLA-대립유전자형 형별이 가능해지고 형별대상의 수가 축적됨에 따라 과거 한국인에서 볼 수 없었던 대립유전자형이 검출될 것으로 예상된다. 결과: 혈청학적인 방법과 ARMS-PCR 방법에 의해 밝혀진 제대혈액의 HLA-B homozygote가 진정한 homozygote인가를 규명하기 위한 연구 도중에 한국인에서는 존재하지 않는다고 알려져 있던 HLA-B*4901을 direct sequencing으로 확인할 수 있었다. 결론: HLA 형별 결과가 장기 생존율 및 GVHD 발생에 영향을 미치는 조혈모세포이식이 증가되고 있으므로, 각 locus별로 blank이거나 homozygote인 경우에는 DNA수준의 HLA-대립유전자형별이 필수적이다. Background: HLA (human leukocytes antigens)-class I genes are highly polymorphic, play many roles in organ and bone marrow transplantain. HLA-B is the most polymorphic in exon 2 and exon 3 of class I locus with 258 alleles. Methods: Until recently, HLA-class I typing has been mainly based on serologic methods. The development of molecular biological techniques make it possible to define the genotypes in HLA genes. HLA-B49, B50, B18, B45, B73 alleles which have been known to be rare or absent in Korean are expected to be found by both the development of HLA genotyping at the DNA level and the accumulation of HLA data. Results: HLA-B genotyping by direct sequencing was performed on cord blood sample which HLA-B serotype was homozygote or blank by ARMS-PCR method. We found HLA- B*4901 allele which was rare in Korean. Conclusion: In order to increase the successful frequencies of stem cell transplantation, HLA genotyping at the DNA levels are necessary in case of blank or homozygous loci.
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B형 간염 바이러스의 만성 감염 및 수직 감염 예방과 HLA 대립유전자와의 연관성
김종현(Jong-Hyun Kim),표철우(Chul-Woo Pyo),허성숙(Seong-Suk Hur),김양겸(Yang-Kyum Kim),고대균(Dae-Kyun Koh),오진희(Jin-Hee Oh),허재균(Jae-Kyun Hur),강진한(Jin-Han Kang),백순영(Soon-Young Paik),유문간(Mun-Gan Rhyu),김금용(Gum-Ryong Ki 대한미생물학회 2003 Journal of Bacteriology and Virology Vol.33 No.3
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