관상동맥 질환에서 CD14 유전자형에 따른 세균 및 Heat Shock Protein에 대한 반응의 차이
The Association between CD14 Polymorphism and Response to Infectious Agents or Heat Shock Protein in Patients with Stable Coronary Artery Disease in Koreans
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목 적 : 만성적인 세균 감염이나 자가 면역 반응이 동맥경화와 연관되어 있다는 주장이 제기되어 왔다. CD14은 lipopolysaccharides (LPS)와 heat shock protein(HSP)의 수용체로 C(-260)→T 다형성이 관상동맥 질환의 위험과 관련되어 있다고 제안되어 왔다. 본 연구에서는 한국인에서 CD14 다형성에 따른 LPS와 HSP에 대한 반응성을 염증표지자를 측정하여 살펴보고자 하였다. 재료 및 방법 : 안정형 관상동맥 환자 48명과 정상 대조군 41명을 대상으로 Chlamydia pneumoniae, Helicobacter pylori 항체 및 인체 HSP60 (hHSP60) 항체 역가를 enzyme-linked immunosorbent assay (ELISA) 방법으로 측정하였다. CD14 유전자형은 중합효소연쇄반응을 이용하여 결정하였고 hs-CRP를 측정하였다. 결 과 : C. pneumoniae 및 H. pylori 항체 양성 여부 및 항체 역가, 그리고 hHSP60에 대한 항체 역가는 안정형 관상동맥 질환의 유무와 유의한 상관관계는 없었다. CD14 유전자형의 분포는 TT 30명(39%), CT 31명(40%), 그리고 CC 16명(21%)이었다. 관상동맥 질환 군에서 TT 유전자형은 38%, 대조군에서는 32%로 TT 유전자형과 관상동맥 질환의 유무와는 유의한 상관관계가 발견되지 않았다(P>0.05). CD14 유전자형에 따라 C. pneumoniae와 H. pylori 감염 및 hHSP60에 따른 반응에 차이가 있는지 여부를 알아보기 위해, 관상동맥 질환 군을 다시 TT 유전자형 군과 non-TT 유전자형 군으로 나누어, 전체적으로 세 군에서 항체 양성률과 역가를 비교하였다(I군: CD14 TT 유전자형을 가진 안정형 관상동맥 환자, II군: CD14 TT 유전자형을 가진 안정형 관상동맥 환자, III군: 정상 대조군). 세 군에서 C. pneumoniae와 H. pylori 항체 양성률 및 hHSP60 항체 역가에는 유의한 차이가 없었다. 세 군 사이에 hs-CRP 값에 유의한 차이가 있었지만, post-Hoc 분석에서 II군의 hs-CRP 값이 I군에 비해 유의하게 높지는 않았다(0.35 [0.1-2.0] mg/L in group II vs. 1.6 [1.1-3.5] mg/L in group I, P>0.05). 결 론 : 본 연구는 한국인에서 CD14 유전자형에 따라 LPS나 HSP에 대한 반응이 유의하게 다르지 않음을 시사한다.
Abstract
Background : CD14 is the receptor for lipopolysaccharides and heat shock protein (HSP), which has been suggested being associated with increased risk of coronary artery disease (CAD). We investigated whether the response to infectious agents or HSP is different according to CD14 polymorphism in Koreans. Materials and Methods : Antibody titers to Helicobacter pylori, Chlamydia pneumoniae, and human HSP60 (hHSP60) were measured in 48 patients with stable CAD and in 41 healthy controls by ELISA. CD14 genotype was determined by PCR and high-sensitivity C-reactive protein (hs-CRP) was measured. Results : Seropositivity to C. pneumoniae and H. pylori, and antibody titer to hHSP60 were not significantly associated with the presence of CAD. CD14 genotype distribution was 31 TT (35%), 43 CT (48%), and 15 CC (17%). To compare the response to the infectious organism and hHSP60, we divided study population into 3 groups; CAD patients with non-TT genotype (group I, n=30), CAD patients with TT genotype (group II, n=18), and normal controls (group III, n=41). Seropositivity to C. pneumoniae and H. pylori, and antibody titer to hHSP60 were not significantly different among 3 groups. Though hs-CRP level was significantly different among 3 groups, post-Hoc analysis showed that hs-CRP level was not significantly different between group I and group II (group I: 1.6[1.1-3.5] mg/L and group II: 0.35[0.1-2.0] mg/L). Conclusions : This study suggests that the inflammatory responses to infectious organisms and HSP do not differ according to the CD14 genotype in Koreans.
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