GENETIC SUSCEPTIBILITY FACTORS IN PORPHYRIA CUTANEA TARDA (PCT)

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 迟发性皮肤卟啉症（PCT）发生在某些受某些环境和遗传易感因素影响的个体中，并表现为皮肤光敏性和肝损伤。 易感因素包括丙型肝炎、饮酒、吸烟、铁超负荷、艾滋病毒、雌激素和遗传性部分UROD缺乏症。 为什么PCT只在少数具有这些易感因素的个体中发展，其中许多是相对常见的，尚不清楚，其他影响-最有可能是额外的遗传差异-仍有待确定。 我们将研究新的假设，即代谢外来化学物质的酶的遗传差异可能有助于开发PCT。 目标1. 至少120例有充分记录的PCT患者将入组病例对照研究，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在特定酶（例如CYP 1A 1、CYP 1A 2、CYP 2 E1、GSTM 1和GSTT 1）中的特定遗传差异。 目标二。 将使用逻辑回归模型检查与临床特征、已知易感因素、治疗应答和复发频率的关联。 目标3。 这些患者和匹配对照的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，作为将来研究PCT其他遗传易感因素的资源。 将对结果进行总结和统计分析，以将PCT组与两个对照组进行比较。 这项研究和随后的项目将有助于更好地了解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.