Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Human Leukocyte Antigen(HLA) Genotypes and Thyroid Autoimmunity in Korean Patients with Type 1 Diabetes

한국인 제 1형 당뇨병 환자들의 HLA 유전자형 및 자가면역성 갑상선 질환의 병발 양상

  • Kang, So Young (Department of Pediatrics, Dankook University College of Medicine) ;
  • Shin, Chung Ho (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yang, Sei Won (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Park, Myoung Hee (Department of Laboratory Medicine, Seoul National University College of Medicine) ;
  • Yu, Jeesuk (Department of Pediatrics, Dankook University College of Medicine)
  • 강소영 (단국대학교 의과대학 소아과학교실) ;
  • 신충호 (서울대학교 의과대학 소아과학교실) ;
  • 양세원 (서울대학교 의과대학 소아과학교실) ;
  • 박명희 (서울대학교 의과대학 검사의학교실) ;
  • 유지숙 (단국대학교 의과대학 소아과학교실)
  • Received : 2005.02.23
  • Accepted : 2005.04.07
  • Published : 2005.06.15
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Abstract

Purpose : This study analyzed the expression of HLA-DR and DQ genotypes and anti-thyroid autoantibodies[anti-thyroid peroxidase(TPO) and anti-thyroglobulin(TG) antibodies] in Korean patients with type 1 diabetes(T1DM) to investigate the susceptible HLA alleles to T1DM in Korea and the prevalence of thyroid autoantibodies and their significance for the development of thyroid disorders. Methods : A total of 59 Korean patients with type 1 diabetes[26 males, median age 13.7 years(range 5.7-29.9 years), diabetes duration 7.6 years(-1.7-22.5 years)] were enrolled in this study, and 200 healthy Koreans without a family history of diabetes were selected as a normal control for the comparison of HLA genotypes. Seventeen patients with anti-TPO or anti-TG were followed [median duration 3.96 years(1 day-10.7 years)] with measurement of anti-TPO, anti-TG, $T_3$, $T_4$ or free $T_4$, TSH levels and physical examinations. HLA-DR and DQ genotyping were done by PCR-SSO, PCR-SSCP, PCR-RFLP and PCR-SSP methods. Results : HLA analysis showed higher frequencies of HLA-DRB1*0301, *090102 and DQB1*0201, *030302 alleles, DRB1*0301/*090102, *090102/*090102 and DQB1 *0201/*030302, *030302/*030302, *0201/ *0302 genotypes in T1DM patients compared to controls(Pc<0.05). Fifteen(25.4 percent) had anti-TPO antibody, 12(20.3 percent) had anti-TG, 17(28.8 percent) had either autoantibody and 10(16.9 percent) had both autoantibodies. No clinical or subclinical hypothyroidism developed during follow-up after the first detection of anti-thyroid autoantibody. There was no significant correlation between thyroid autoimmunity and gender, onset age of T1DM, and diabetes duration, respectively(P>0.05). Conclusion : We thought this unique HLA-DR, DQ allele distribution might be an important factor for the low incidence of T1DM in Korea. And a high prevalence of thyroid autoantibodies in these populations suggests examinations of thyroid antibodies should be performed regularly. Optimal age for the initial screening and the frequency of re-screening for associated thyroid autoimmune diseases in T1DM remains to be determined through prospective follow-up.

목 적 : 본 연구는 한국인 제 1형 당뇨병 환자들에서 HLADR과 DQ 유전자형 및 갑상선 자가항체(항 TPO 자가항체와 항 thyroglobulin 자가항체)를 분석함으로써, 한국인 제 1형 당뇨병과 관련 있는 특정 HLA 유전자형을 알아보고자 하였고, 이들 제 1형 당뇨병 환자들에서의 갑상선 자가항체의 유병률, 갑상선 질환으로의 발현 및 이들 자가면역성 갑상선염과 HLA 유전자형과의 관련성을 알아보고자 하였다. 방 법 : 총 59명[남아 26명, 검사시 연령 13.7세(5.7-29.9세), 당뇨병 유병기간 7.6년(-1.7-22.5년)]의 제 1형 당뇨병 환자를 대상으로 하였고, 갑상선 질환의 병력 및 가족력이 없는 건강한 200명의 한국인의 HLA 유전자형을 대조군으로 하였다. 59명의 환자 중 갑상선 자가항체 양성인 17명은 중앙기간 3.96년(1일-10.7년) 동안 진찰 및 anti-TPO, anti-TG, $T_3$, $T_4$ 또는 free $T_4$, TSH 검사를 시행하면서 추적 관찰하였다. HLA-DR과 DQ의 유전자 분석은 PCR-SSO, PCR-SSCP, PCR-RFLP 및 PCR-SSP 방법을 이용하였다. 결 과 : 제 1형 당뇨병 환자들에서 대조군에서보다 HLADRB1*0301, *090102, DQB1*0201, *030302, DRB1*0301/*090102, DRB1*090102/*090102, DQB1*0201/*030302, *030302/*030302, *0201/*0302의 빈도가 높았다(Pc<0.05). 15명(25.4%)에서 TPO에 대한 자가항체 양성이었고, 12명(20.3%)에서 TG 자가항체 양성이었으며, 17명(28.8%)은 두 가지 항체 중 한 가지 이상의 항체를 갖고 있었다. 10명(16.9%)은 두 종류의 항체를 모두 갖고 있었다. 갑상선 항체 양성을 보인 이후부터의 추적기간 동안 갑상선기능저하증을 보인 경우는 없었다. 3명(5.1%)의 여아에서 당뇨병 진단 전 또는 후에 갑상선기능항진증이 진단(8.5세, 11세, 13.2세)되었다. 갑상선 자가항체의 유무 및 각각의 항체 종류에 따른 대상군간의 제 1형 당뇨병 진단연령, 갑상선 검사시 연령, 당뇨병 유병기간 및 성별의 차이는 보이지 않았다(P>0.05). 결 론 : 한국인에서는 HLA-DRB1*0301, *090102, DQB1*0201, *030302, DRB1*0301/*090102, *090102/*090102, DQB1*0201/*030302, *030302/*030302, *0201/*0302 등이 제 1형 당뇨병에 대한 감수성 인자였고, 코카시안과는 다른 HLA-DR 및 DQ의 분포가 한국인에서 제 1형 당뇨병의 발생률이 낮은 이유중의 하나를 차지하리라고 생각되었다. 한편, 제 1형 당뇨병 환자들에서 갑상선 자가항체 양성률은 28.8%였고, 이는 한국인 제 1형 당뇨병 환자에서도 갑상선 자가항체 검사가 규칙적으로 시행되어야 함을 시사한다고 하겠다. 한국인 제 1형 당뇨병 환자에서 자가면역성 갑상선 질환에 대한 선별검사 시작 시기와 횟수 등에 대해서는 이들 환자들의 장기적인 추적관찰을 통해 추후 좀더 연구가 필요하리라 생각된다.

Keywords

Acknowledgement

Supported by : 단국대학교

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