Maliarik M J, Rybicki B A, Malvitz E, Sheffer R G, Major M, Popovich J, Iannuzzi M C
Division of Pulmonary and Critical Care Medicine and Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan, USA.
Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1566-70. doi: 10.1164/ajrccm.158.5.9804123.
The angiotensin-converting enzyme (ACE) has been implicated in the pathophysiology of sarcoidosis. Serum ACE levels in normal and sarcoidosis patients are influenced by an insertion (I)/deletion (D) polymorphism in the ACE gene. To elucidate the role of this ACE gene polymorphism in sarcoidosis, we conducted a case-control study in African Americans and Caucasians. The ACE gene (I/D) polymorphism did not differ between 60 Caucasian cases and 48 control subjects (p = 0.577). In contrast, a comparison of 183 African-American cases and 111 control subjects resulted in a marked difference in genotypic distributions (p = 0.005). In African Americans, the risk for sarcoidosis was 1.30 (95% confidence interval [CI] = 0.72 to 2. 36) for ID heterozygotes, and 3.17 (95% CI = 1.50 to 6.71) for deletion/deletion (DD) homozygotes. The risk associated with the DD homozygotes was even greater in African Americans when cases were restricted to those with a positive family history (odds ratio = 4. 83; 95% CI = 1.86 to 12.59). Further analyses of African-American cases showed that the ACE genotype was not associated with disease severity, extrathoracic involvement, or overall radiographic change 2 to 4 yr after diagnosis. We did find a moderate association between the II genotype and radiographic progression (OR = 2.97; 95% CI = 1.01 to 8.76). Our results suggest the ACE genotype may play a more important role in sarcoidosis susceptibility and progression in African Americans than Caucasians.
血管紧张素转换酶（ACE）与结节病的病理生理学有关。正常人和结节病患者的血清ACE水平受ACE基因插入（I）/缺失（D）多态性的影响。为了阐明这种ACE基因多态性在结节病中的作用，我们在非裔美国人和白种人中进行了一项病例对照研究。60例白种人病例和48例对照受试者之间的ACE基因（I/D）多态性没有差异（p = 0.577）。相比之下，183例非裔美国人病例和111例对照受试者的基因型分布存在显著差异（p = 0.005）。在非裔美国人中，ID杂合子患结节病的风险为1.30（95%置信区间[CI]=0.72至2.36），缺失/缺失（DD）纯合子的风险为3.17（95%CI = 1.50至6.71）。当病例仅限于有家族史阳性的非裔美国人时，与DD纯合子相关的风险更大（优势比=4.83；95%CI = 1.86至12.59）。对非裔美国人病例的进一步分析表明，ACE基因型与疾病严重程度、胸外受累或诊断后2至4年的总体影像学变化无关。我们确实发现II基因型与影像学进展之间存在中度关联（OR = 2.97；95%CI = 1.01至8.76）。我们的结果表明，ACE基因型在非裔美国人结节病易感性和进展中可能比白种人起更重要的作用。
