Identification of Genetic Risk Factors for BPH.

前列腺增生症遗传风险因素的鉴定。

• 批准号: 7870800
• 负责人: WILLIAM B ISAACS
• 金额: $ 34.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7870800
• 关键词: Alleles; Benign Prostatic Hypertrophy; Biochemical; Biological; Candidate Disease Gene; Classification; Clinical; Complex; Data; Development; Disease; Disease Association; Disease susceptibility; Etiology; Evaluation; Family; Follow-Up Studies; Frequencies; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genotype; Goals; Health Professional; Investigation; Linkage Disequilibrium; Malignant neoplasm of prostate; Maryland; Molecular; Molecular Analysis; Molecular Genetics; Nature; Pathogenesis; Pathologic; Pathway interactions; Population; Population Study; Predisposition; Preventive; Risk; Role; Single Nucleotide Polymorphism; Staging; Technology; Testing; Therapeutic; Twin Studies; Variant; base; case control; disorder risk; follow-up; genetic association; genetic risk factor; genetic variant; genome wide association study; genome-wide; genotyping technology; men; novel; success; tool; translational approach

Despite years of intensive investigations, the etiology of benign prostatic hyperplasia (BPH) is still uncertain. To date, however, the powerful tools of molecular genetics have not been extensively used to investigate these mechanisms. In particular, genetic association is a powerful approach to identify genes and/or genetic loci that confer disease susceptibility. Family and twin studies by our group and others have provided strong evidence for genetics as an important factor in the development of BPH. These intriguing findings of a genetic susceptibility to BPH suggests that there are germline sequence variants in the genome predisposing to the disease. We feel that there is enough evidence for an important genetic component of BPH to justify a systematic search to identify BPH susceptibility alleles, and that progress in genome wide association technology makes such a search highly lil<ely to yield valuable results. Single nucleotide polymorphisms (SNPs) may be directly associated with BPH risk or indirectly associated with BPH risk through linkage disequilibrium (LD) with a causal sequence variant. These risk-associated SNPs will have different genotype frequencies among men with or without BPH and can be detected using genetic association studies. We propose to test the hypothesis that commonly occurring genetic variants exist in the population which are associated with increases in risk for BPH. The goal ofthis study is to identify and characterize these BPH susceptibility loci. To accomplish this goal, we propose to carry out a genome wide association study and confirming follow up analyses in men with and without BPH. Once identified, these loci will provide the basis for functional studies to characterize the role of these loci in the development of BPH. Understanding the molecular etiology ofthis disease will have important clinical consequences in terms of developing novel preventive and therapeutic approaches for this common disease.

尽管进行了多年的深入研究，但良性前列腺增生（BPH）的病因仍然不确定。 然而，迄今为止，尚未广泛用于调查分子遗传学的强大工具 这些机制。特别是，遗传关联是一种识别基因和/或遗传的强大方法 赋予疾病易感性的基因座。我们小组和其他人的家庭和双胞胎研究提供了强大的 遗传学作为BPH发展的重要因素的证据。这些有趣的发现 对BPH的遗传敏感性表明基因组中存在种系序列变异 易感性疾病。我们认为有足够的证据表明 BPH证明系统搜索是合理的，以识别BPH的易感性等位基因，并且基因组范围的进展 协会技术使这样的搜索高度lil <Ely，以产生宝贵的结果。单核苷酸 多态性（SNP）可能与BPH风险直接相关或与BPH风险间接相关 通过具有因果序列变体的连锁不平衡（LD）。这些与风险相关的SNP会有 有或没有BPH的男性中的不同基因型频率，可以使用遗传检测 协会研究。 我们建议检验以下假设：种群中存在常见的遗传变异 与BPH风险增加有关。这项研究的目的是识别和表征这些BPH 敏感位点。为了实现这一目标，我们建议进行一项基因组广泛的关联研究和 确认有和没有BPH的男性的后续分析。一旦确定，这些基因座将提供基础 用于功能研究以表征这些基因座在BPH发展中的作用。了解 这种疾病的分子病因将在发展新颖的方面产生重要的临床后果 这种常见疾病的预防和治疗方法。