Bulaj Z J, Phillips J D, Ajioka R S, Franklin M R, Griffen L M, Guinee D J, Edwards C Q, Kushner J P
Departments of Medicine, Pharmacology, and Pathology, the University of Utah School of Medicine, and the Latter Day Saints Hospital, Salt Lake City, UT, USA.
Blood. 2000 Mar 1;95(5):1565-71.
Inherited and acquired factors have been implicated in the pathogenesis of porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis. This study, comprising 108 patients with PCT, was intended to define the role of hemochromatosis gene (HFE) mutations in the expression of PCT and to determine the contribution of acquired factors including alcohol, hepatitis C virus (HCV), and estrogen. The 2 known HFE mutations, cysteine 282 tyrosine (Cys282Tyr) and histidine 63 asparagine (His63Asp), were detected by polymerase chain reaction, and anti-HCV immunoglobulin G was detected serologically. Liver biopsies were graded for iron content, inflammation, and fibrosis. Estimates of alcohol and estrogen use were based on a questionnaire. Of the PCT patients tested, 19% were homozygous for the Cys282Tyr mutation; controls were equal to 0.5%. The compound heterozygous genotype was detected in 7% of the PCT patients; controls were less than 1%. The transferrin saturation, serum ferritin, and liver iron burden of all PCT patients were higher than those of nonporphyric controls. The highest values were found in PCT patients homozygous for the Cys282Tyr mutation. Of the patients studied, 59% were HCV positive (compared with 1.8% of the population), and 46% consumed more than 70 g of alcohol daily. Of the female patients, 63% were ingesting estrogens. Hepatic damage was most marked in patients with the Cys282Tyr/Cys282Tyr genotype who had HCV and drank heavily. Homozygosity for the Cys282Tyr mutation and HCV are the greatest risk factors for expression of PCT, and in most patients, more than 1 risk factor was identified. It was common for patients with HCV to consume alcohol. Patients with PCT should be screened for HFE mutations and for HCV. (Blood. 2000;95:1565-1571)
遗传性和获得性因素与迟发性皮肤卟啉症（PCT）的发病机制有关，PCT是一种以光敏性皮炎和肝铁沉积为特征的疾病。这项研究纳入了108例PCT患者，旨在明确血色素沉着症基因（HFE）突变在PCT表达中的作用，并确定包括酒精、丙型肝炎病毒（HCV）和雌激素在内的获得性因素的影响。通过聚合酶链反应检测2种已知的HFE突变，即半胱氨酸282酪氨酸（Cys282Tyr）和组氨酸63天冬酰胺（His63Asp），并通过血清学检测抗HCV免疫球蛋白G。对肝活检标本进行铁含量、炎症和纤维化分级。酒精和雌激素使用情况的评估基于一份问卷。在接受检测的PCT患者中，19%为Cys282Tyr突变纯合子；对照组为0.5%。7%的PCT患者检测到复合杂合基因型；对照组低于1%。所有PCT患者的转铁蛋白饱和度、血清铁蛋白和肝脏铁负荷均高于非卟啉症对照组。Cys282Tyr突变纯合子的PCT患者中这些指标值最高。在所研究的患者中，59%为HCV阳性（相比人群中的1.8%），46%每天饮酒超过70克。在女性患者中，63%正在服用雌激素。Cys282Tyr/Cys282Tyr基因型且感染HCV并大量饮酒的患者肝损伤最为明显。Cys282Tyr突变纯合子和HCV是PCT表达的最大危险因素，并且在大多数患者中，可识别出不止一种危险因素。HCV患者饮酒很常见。PCT患者应筛查HFE突变和HCV。（《血液》。2000年；95：1565 - 1571）
