Genetics of Interstitial Cystitis

间质性膀胱炎的遗传学

• 批准号: 6803956
• 负责人: JOHN W WARREN
• 金额: $ 62.49万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803956
• 关键词: alleles; clinical research; disease /disorder etiology; epidemiology; family genetics; genetic registry /resource /referral center; genetic susceptibility; genotype; human genetic material tag; human subject; interstitial cystitis; linkage mapping; medical outreach /case finding; pain; patient oriented research

DESCRIPTION (provided by applicant): Interstitial cystitis (IC) comprises severe bladder pain and urinary frequency and urgency, has objective diagnostic findings, and its pathogenesis is unknown. We have shown that first-degree relatives of IC patients have a relative risk of > 16. That this familial aggregation is not solely an environmental effect is reflected by our further findings of significantly greater concordance among monozygotic than dizygotic twins and occurrence of IC in 2nd and 3rd degree relatives who presumably have not shared households. Hypothesizing that alleles for IC are inherited in these families, we will recruit multiplex families, i.e. those with greater than or equal too 2 first degree relatives who meet NIDDK criteria for IC, via a national recruitment campaign directed at urologists, employing the Internet, and collaborating with the Interstitial Cystitis Association. Pedigrees will be constructed with family members assigned to intermediate categories of IC. We will perform linkage analysis seeking loci of susceptibility to IC. We estimate that >900 probands will be evaluated. Reasonable assumptions of eligibility and volunteer rates suggest we will enroll >450 multiplex families with >2400 family members donating DNA. To date, a survey has already identified 101 potential probands; 143 unsolicited, additional potential probands have contacted us. Parametric, non-parametric, and conditional analyses will be performed with attention to subgroups to maximize homogeneity and to intermediate categories to avoid misclassification. The large number of participants will provide substantial power. We will finely map linkage regions and perform family-based linkage and association tests. In parallel we will help to discover additional multiplex families for extension/replication studies. These data on pedigrees and genotypes and stored DNA, from properly informed participants, will be a valuable resource. The identification of alleles of susceptibility to IC may reveal clues to pathogenesis, clinical therapy, preventive strategy, and possibly gene therapies.

描述（由申请人提供）：间质性膀胱炎（IC）包括严重的膀胱疼痛，尿频和紧迫性，具有客观的诊断结果，其发病机理尚不清楚。我们已经表明，IC患者的一级亲戚的相对风险> 16。这种家族聚集不仅是环境效应的反映，我们进一步的单卵双胞胎的进一步研究结果反映了单卵双胞胎的一致性明显更大的一致性，而IC在2nd中的发生。大概没有共享家庭的三级亲戚。假设这些家庭在这些家庭中继承了IC等位基因，我们将招募多元化家庭，即具有符合NIDDK标准IC的一级亲戚超过或平等的人，通过针对泌尿科医生，雇用互联网的国家招聘运动，并与间质性膀胱炎协会合作。谱系将与分配给IC中间类别的家庭成员建造。我们将执行链接分析，以寻求对IC敏感的基因座。我们估计将评估> 900个概率。合理的资格和志愿者费率的合理假设表明，我们将招募> 450个多重多重家族，其中> 2400个家庭成员捐赠了DNA。迄今为止，一项调查已经确定了101个潜在概率。 143未经请求的其他潜在概率已与我们联系。参数，非参数和条件分析将以对亚组的注意进行，以最大程度地提高同质性和中间类别，以避免错误分类。大量参与者将提供实质性的力量。我们将精细绘制链接区域并执行基于家庭的联系和关联测试。同时，我们将帮助发现其他多重家族进行扩展/复制研究。这些有关血统和基因型以及来自适当知情参与者的DNA的数据将是宝贵的资源。识别IC易感性的等位基因可能揭示了对发病机理，临床疗法，预防策略以及可能的基因疗法的线索。