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조산아 기관지폐이형성증과 Tumor Necrosis Factor-α 유전자 다 형성과의 연관성

Association between Tumor Necrosis Factor-α Gene Polymorphism and Bronchopulmonary Dysplasia in Preterm Infants

김병일|최중환|장윤환|김한석|조희승
대한신생아학회 (THE KOREAN SOCIETY OF NEONATOLOGY)|2011.05|Neonatal medicine|제18권 제1호|pp. 42-48

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Premature infantBronchopulmonary dysplasiaGenetic polymorphismTumor necrosis factor-α

초록

목적: 기관지폐이형성증(bronchopulmonary dysplasia,BPD)의 발생에는 폐의 염증반응이 중요하게 작용한다. Tumor necrosis factor-α (TNF-α)는 대표적인 proinflammatory cytokine으로, TNF-α 고생산 부위의 단일염기다형성과 BPD 발생 사이의 연관성을 알아보고자 하였다. 방법: 2006년 1월부터 12월까지 서울대학교병원에서 출생하여 신생아중환자실에 입원한 재태주령 32주 미만이면서 출생체중 1,500 g 미만의 미숙아 93예를 대상으로, 실시간 중합효소연쇄반응을 이용하여, TNF-α 유전자 촉진자 5개 부위(-1031T/C,-863C/A, -857C/T, -308G/A, -238G/A)의 단일염기다형성을분석하였다. 결과: BPD 군은 전체연구대상93예 중에서 38예로40.9%에해당하였다. BPD 군에서 대조군보다 재태연령(27+5±2+0 wk vs. 29+2±1+4 wk, P<0.0001)과 출생체중(990±270 g vs. 1,220±230 g, P<0.0001)이 낮고, 신생아 호흡곤란증후군(71.1% vs. 49.1%, P=0.035) 과 동맥관개존(71.1% vs. 50.9%, P=0.052) 의발생빈도가 높아서 두 군간의 임상적 특성에는 차이가 있었다. 그러나 TNF-α 유전자 단일염기다형성 분석에서는, 각각의TNF-α 대립유전자의 빈도와 일배체형의 분포 모두가 BPD 군과 대조군 사이에 차이를 보이지 않았다. 결론: 한국인 조산아에서는, TNF-α 유전자 다형성보다는 임상적인 위험인자가 BPD 발생에 중요하게 작용하였다.

Abstract

Purpose: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α). We investigated the relationship between susceptibility to BPD and TNF-α promoter polymorphisms to identify genetic factors of the disease. Methods: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-α genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-α gene were determined using Taqman^®-based allelic discrimination assays. Results: Gestational age (27^(+5)±2^(+0) wk vs. 29^(+2)±1^(+4) wk, P<0.0001) and birth weight (990±270 g vs. 1,220±230 g, P<0.0001)were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%,P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-α gene did not show differences between the BPD group and the control group. Conclusion: TNF-α promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants.

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