GENETIC SUSCEPTIBILITY FACTORS IN PORPHYRIA CUTANEA TARDA (PCT)

迟发性皮肤卟啉症 (PCT) 的遗传易感因素

• 批准号: 7952156
• 负责人: KARL ELMO ANDERSON
• 金额: $ 1.78万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952156
• 关键词: Alcohol consumption; CYP1A2 gene; CYP2E1 gene; Case-Control Studies; Chemicals; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Control Groups; Controlled Study; DNA; Enrollment; Enzymes; Estrogens; Frequencies; Funding; Future; GSTM1 gene; GSTT1 gene; Genetic; Genetic Predisposition to Disease; Grant; HIV; Hepatitis C; Individual; Inherited; Institution; Iron Overload; Lead; Liver; Logistic Regressions; Lymphocyte; Matched Group; Modeling; Patients; Photosensitivity; Porphyria Cutanea Tarda; Predisposition; Relapse; Research; Research Personnel; Resources; Skin; Smoking; Source; United States National Institutes of Health; novel; treatment response

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 迟发性皮肤卟啉症 (PCT) 发生在某些易受某些环境和遗传易感因素影响的个体中，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、铁超载、HIV、雌激素和遗传性 UROD 部分缺乏。 为什么 PCT 仅在少数具有这些易感因素的个体中发生（其中许多因素相对常见）尚不清楚，并且其他影响（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。 目标 1. 至少 120 名有充分记录的 PCT 患者将被纳入病例对照研究，该研究将包括两组不同的匹配对照。 将分离 DNA 和淋巴细胞，并研究患者和对照的特定酶（例如 CYP1A1、CYP1A2、CYP2E1、GSTM1 和 GSTT1）的特定遗传差异。 目标 2. 将使用逻辑回归模型检查与临床特征、已知易感因素、治疗反应和复发频率的关联。 目标 3. 来自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存储，作为未来研究 PCT 其他遗传易感因素的资源。 对结果进行总结和统计分析，以比较 PCT 组与两个对照组。 这项研究和随后的项目将有助于更好地理解 PCT。