GENETIC SUSCEPTIBILITY FACTORS IN PORPHYRIA CUTANEA TARDA (PCT)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 迟发性皮肤卟啉病(Porporria cutanea tarda，PCT)是在某些环境和遗传易感因素的作用下发生的，表现为皮肤光敏和肝脏损害。易感因素包括丙型肝炎、饮酒、吸烟、铁超载、艾滋病毒、雌激素和遗传性UROD部分缺陷。为什么PCT只在少数具有这些易感因素的个体中发生，其中许多是相对常见的，尚不清楚，其他影响--很可能是额外的遗传差异--仍有待确定。我们将研究这一新的假设，即代谢外来化学物质的酶的遗传差异可能有助于PCT的发展。 目的1.至少120名有良好记录的PCT患者将参加病例对照研究，该研究将包括两组不同的匹配对照。将分离DNA和淋巴细胞，并研究患者和对照组特定酶(例如，CYP1A1、CYP1A2、CYP2E1、GSTM1和GSTT1)的特定遗传差异。 目的2.用Logistic回归模型分析临床特征、已知易感因素、治疗反应和复发频率之间的关系。 目的3.这些患者和配对对照的DNA和淋巴细胞，以及有关临床特征和已知易感因素的信息将被储存起来，作为未来研究PCT其他遗传易感因素的资源。 结果将总结和统计分析，比较PCT组和两个对照组。这项研究和随后的项目将有助于更好地理解PCT。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Porphyria cutanea tarda (PCT) develops in some individuals who are predisposed by certain environmental and inherited susceptibility factors, and is manifested by skin photosensitivity and liver damage. Susceptibility factors include hepatitis C, alcohol use, smoking, iron overload, HIV, estrogens and an inherited partial deficiency of UROD. Why PCT develops in only a few individuals with these susceptibility factors, many of which are relatively common, is not known, and additional influences - most likely additional inherited differences - remain to be identified. We will investigate the novel hypothesis that genetic differences in enzymes that metabolize foreign chemicals may contribute to developing PCT. Aim 1. At least 120 patients with well documented PCT will be enrolled in a case-control study that will include two different groups of matched controls. DNA and lymphocytes will be isolated, and patients and controls studied for specific genetic differences in specific enzymes (e.g.CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1). Aim 2. Associations with clinical features, known susceptibility factors, treatment response and frequency of relapse will be examined using logistic regression models. Aim 3. DNA and lymphocytes from these patients and matched controls, and information regarding clinical features and known susceptibility factors will be stored as a resource for future studies of additional genetic susceptibility factors for PCT. Results will be summarized and analyzed statistically to compare the PCT group with the two control groups. This study and projects which follow will lead to a better understanding of PCT.