Selenoprotein SNPs and Haplotypes in HIV and Cancer

HIV 和癌症中的硒蛋白 SNP 和单倍型

• 批准号: 6651589
• 负责人: CHARLES B FOSTER
• 金额: $ 15.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651589
• 关键词: DNA footprinting; HIV infections; Kaposi's sarcoma; NAD(P)H oxidoreductase; antisense nucleic acid; cancer risk; clinical research; functional /structural genomics; gel mobility shift assay; genetic polymorphism; genetic susceptibility; glutathione peroxidase; human genetic material tag; human tissue; luciferin monooxygenase; molecular cloning; nucleic acid sequence; pathologic process; polymerase chain reaction; postmortem; selenium; selenoprotein

DESCRIPTION (provided by applicant): Selenium deficiency has been associated with an increased risk of prostate, esophageal, gastric, lung, thyroid and ovarian cancer, colonic adenomas, and hepatocellular carcinoma. Selenium deficiency has also been correlated with accelerated disease progression and increased mortality in both HIV-infected children and adults. In animal models selenium deficiency is associated with enhanced oxidative stress, anthracycline induced cardiotoxicity and virulent Coxsackie virus infection. In humans selenium supplementation may reduce the rate of specific cancers including lung, prostate, and colon. In the form of selenocysteine (the 21st amino acid), selenium is incorporated into the primary structure of at least 16 human proteins, most of which have important antioxidant properties. Given the important role that selenium and selenoenzymes play in protecting against oxidative stress, it is possible that genetic variations in selenoenzymes may be risk factors for specific cancers or for severe inflammatory or infectious complications of disease. To help unravel the role of selenium in cancer and infectious diseases, this grant proposes to identify and confirm novel SNPs in selenium containing genes, with a focus on glutathione peroxidase and thioredoxin reductase. Functional studies will define the biologic importance of SNPs and haplotypes. The generated data will provide a critical foundation for interpreting clinical association studies designed to correlate genetic variants in selenoenzyme genes with risk of HIV progression or of developing cancer.

描述（由申请人提供）：缺硒与前列腺癌、食道癌、胃癌、肺癌、甲状腺癌和卵巢癌、结肠腺瘤和肝细胞癌的风险增加有关。 缺硒还与艾滋病毒感染儿童和成人的疾病进展加速和死亡率增加相关。 在动物模型中，缺硒与氧化应激增强、蒽环类药物诱导的心脏毒性和剧毒柯萨奇病毒感染有关。 对于人类来说，补充硒可以降低特定癌症的发病率，包括肺癌、前列腺癌和结肠癌。 硒以硒代半胱氨酸（第 21 个氨基酸）的形式融入至少 16 种人类蛋白质的一级结构中，其中大多数具有重要的抗氧化特性。 鉴于硒和硒酶在防止氧化应激方面发挥着重要作用，硒酶的遗传变异可能是特定癌症或严重炎症或感染性疾病并发症的危险因素。 为了帮助揭示硒在癌症和传染病中的作用，这笔赠款建议识别和确认含硒基因中的新 SNP，重点是谷胱甘肽过氧化物酶和硫氧还蛋白还原酶。 功能研究将定义 SNP 和单倍型的生物学重要性。 生成的数据将为解释临床关联研究提供重要基础，这些临床关联研究旨在将硒酶基因的遗传变异与艾滋病毒进展或患癌症的风险相关联。