Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Analysis of HLA in Patients with Obstructive Sleep Apnea Syndrome

폐쇄성 수면무호흡증후군 환자에서 사람백혈구항원 분석

  • Lee, Sang Haak (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Kim, Chi Hong (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Ahn, Joong Hyun (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Kang, Ji Ho (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Kim, Kwan Hyoung (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Song, Jeong Sup (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Park, Sung Hak (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Moon, Hwa Sik (Department of Internal Medicine, The Catholic University of Korea, College of Medicine) ;
  • Choi, Hee Baeg (Department of Microbiology, The Catholic University of Korea, College of Medicine) ;
  • Kim, Tai Gyu (Department of Microbiology, The Catholic University of Korea, College of Medicine) ;
  • Choi, Young Mee (Department of Internal Medicine, The Maryknoll Hospital)
  • 이상학 (가톨릭대학교 의과대학 내과학교실) ;
  • 김치홍 (가톨릭대학교 의과대학 내과학교실) ;
  • 안중현 (가톨릭대학교 의과대학 내과학교실) ;
  • 강지호 (가톨릭대학교 의과대학 내과학교실) ;
  • 김관형 (가톨릭대학교 의과대학 내과학교실) ;
  • 송정섭 (가톨릭대학교 의과대학 내과학교실) ;
  • 박성학 (가톨릭대학교 의과대학 내과학교실) ;
  • 문화식 (가톨릭대학교 의과대학 내과학교실) ;
  • 최희백 (가톨릭대학교 의과대학 미생물학교실) ;
  • 김태규 (가톨릭대학교 의과대학 미생물학교실) ;
  • 최영미 (메리놀병원 내과)
  • Received : 2005.04.04
  • Accepted : 2005.08.29
  • Published : 2005.09.30
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Abstract

Background : Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. Methods : Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. Results : The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLADRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index >45) than in the controls (p<0.05). Conclusion : This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS.

연구배경 : 폐쇄성 수면무호흡증후군은 다양한 원인에 의해 발생하게 된다. 주된 위험요소로는 비만과 좁은 상기도, 비정상적인 머리-얼굴 구조 등이 알려져 있으며 유전적 요인 또한 가족내 집단적 발생하였다는 보고들에 의해 뒷받침되고 있다. 본 연구에서 저자들은 HLA검사를 통하여 폐쇄성 수면무호흡증후군에서 유전학적인 배경을 규명하고자 하였다. 방 법 : 철야 수면다원검사로 진단한 25명의 폐쇄성 수면무호흡증후군 환자 (여자 1명과 남자 24명, 연령 30-66세)를 대상으로 하였으며 대조군은 200명의 건강한 한국인으로 하였다. HLA-A와 -B 대립유전자의 검사는 미세세포독성검사로 시행하였고 HLA-DRB1 유전자의 두번째 엑손의 다형성에 대한 분석은 PCRSSOP방법을 이용하여 시행하였다. 결 과 : HLA-A11 대립유전자의 빈도는 폐쇄성 수면무호흡증후군 환자군에서 대조군에 비해 유의하게 감소되어 있었다 (p<0.05). HLA-B 대립유전자의 빈도는 양군간에 유의한 차이가 없었다. HLA-DRB1 유전자의 다형태 분석에서는 DRB1*09의 빈도가 폐쇄성 수면무호흡환자군에서 대조군에 비해 유의하게 증가되어 있었다 (p <0.05). 환자군을 무호흡지수 45를 기준으로 경-중등증군과 중증군으로 나누어 대조군과 비교하였을 때 중증군에서 HLA-DRB1*08의 빈도가 유의하게 증가되어 있었다 (p <0.05). 결 론 : 한국의 폐쇄성 수면무호흡증후군 환자에서 HLAA11과 DRB1*09가 폐쇄성 수면무호흡증후군과 관련되어 있고, HLA-DRB1*08이 이 질환의 중증도와 연관되어 있음을 알 수 있었다. 이상의 결과는 폐쇄성 수면 무호흡 증후군의 발생뿐 아니라 경중도 여부에도 유전적인 요소가 중요한 역할을 한다는 것을 시사한다.

Keywords

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