Folate and vitamin B12 metabolism in neural tube defects

神经管缺陷中的叶酸和维生素 B12 代谢

• 批准号: 6430092
• 负责人: Lawrence C Brody
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6430092
• 关键词: aminoacid metabolism; clinical research; folate; genetic susceptibility; homocysteine; human genetic material tag; methionine; molecular pathology; neoplasm /cancer genetics; spina bifida; vitamin B12; vitamin metabolism

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Changes in folate metabolism are correlated tumor formation and birth defects. Folate genes are also involved in the methylation of DNA. We are searching for genetic variants in genes related to folate, methionine and homocysteine metabolism. Individuals affected with cancer or spina bifida will be tested for these variants. Variants found at higher frequency in individuals with disease will help us identify genes associated with risk. More than 30 variants in folate related genes have been identified. A portion of these have been tested in spina bifida families. Initial evidence suggests that two of these new variants are associated with spina bifida risk. We will test the function consequences of these variants in experimental systems. The frequency of the same variants will be measured in individuals with cancer. If confirmed, these two genes will add to our understanding of neural tube defects and cancer risk.

分子发病机理中的研究集中在定义基因的变化，这些基因是遗传性疾病（例如癌症和先天缺陷）的敏感性的基因的变化。叶酸代谢的变化是相关的肿瘤形成和先天缺陷。叶酸基因也参与DNA的甲基化。我们正在寻找与叶酸，蛋氨酸和同型半胱氨酸代谢有关的基因中的遗传变异。患有癌症或脊柱裂的个体将对这些变体进行测试。疾病个体中较高频率发现的变体将有助于我们识别与风险相关的基因。已经确定了30多种相关基因中的30多种变体。其中一部分已在脊柱裂族家庭中进行了测试。最初的证据表明，其中两个新变体与脊柱裂风险有关。我们将测试这些变体在实验系统中的功能后果。同一变体的频率将在癌症个体中进行测量。如果得到证实，这两个基因将增加我们对神经管缺陷和癌症风险的理解。