Planck A, Eklund A, Yamaguchi E, Grunewald J
Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden.
J Intern Med. 2002 Mar;251(3):217-22. doi: 10.1046/j.1365-2796.2002.00946.x.
To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis. DESIGN, SETTINGS AND SUBJECTS: Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA-DR genotyping 67 patients. Serum ACE level (S-ACE) was measured in all controls and 72 patients. Sixty-one patients were classified as chronic or nonchronic after 2 years follow-up. All patients were recruited and followed at our outpatient clinic.
No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S-ACE in patients, whilst in controls S-ACE significantly differed between the ACE genotypes.
This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA-DR alleles in Scandinavian sarcoidosis patients.
研究血管紧张素转换酶(ACE)基因中的插入/缺失(I/D)多态性是否与先前发现对斯堪的纳维亚结节病患者具有预后意义的HLA - DR等位基因相关。这可能有助于了解与这些HLA - DR等位基因相关的特征,例如良好(DR17)或不良(DR14或15)的预后。
设计、地点和研究对象:采用聚合酶链反应(PCR)分析138名受试者(65名对照者和73名结节病患者)ACE编码基因中的I/D多态性,并对67名患者进行HLA - DR基因分型。测定了所有对照者和72名患者的血清ACE水平(S - ACE)。61名患者经过2年随访后被分类为慢性或非慢性。所有患者均在我们的门诊招募并接受随访。
在对照者与患者之间,以及DR17或DR14/15阳性与阴性患者之间,ACE等位基因或基因型均无显著差异。非慢性患者与慢性患者的ACE基因型无差异。ACE基因型倾向于影响患者的S - ACE,而在对照者中,不同ACE基因型的S - ACE存在显著差异。
本研究不支持ACE基因型与结节病或疾病转归之间存在关联。然而,由于被分类为非慢性的DR17阳性患者(19例中的17例)显著多于DR14/15阳性患者(26例中的7例)(P < 0.001),这些结果反而强化了HLA - DR等位基因对斯堪的纳维亚结节病患者的预后重要性。