ADPKD--NATURAL HISTORY AND GENE DISTRIBUTION IN AFRICAN AMERICANS

常染色体显性遗传性多囊肾病是最常见的 美国的遗传性肾病，每400人中就有1人受到影响 1000个人。与糖尿病相关的临床和遗传因素 疾病进展在高加索人群中已经被很好地定义了，但是 其他种族群体的数据很少，包括非洲人- 美国人(AA)。有坊间证据表明，葡萄糖-6- 磷酸脱氢酶(G6PD)缺乏症与镰状细胞性状(SCT) AA、ADPKD患者的不良预后因素分析至少三个 在高加索人群中，独立基因座导致ADPKD。基因 再生障碍性贫血人群中的缺陷(S)尚未确定，也没有 这些ADPKD基因座的频率分布。这个项目的特点是 阿拉巴马州AA人群ADPKD自然病史的确定 特定的临床和遗传因素是否与 肾脏疾病的进展。我们将定义二分式的频率 先前与进展性肾功能不全相关的变量 高加索人(包括性别、高血压、血尿、肾结石、 AA ADPKD患者的尿蛋白尿、囊肿破裂和尿路感染)。频率： 这些变量将在年龄匹配的AA患者中进行比较 无终末期肾病，且与终末期肾病发病年龄相关。另外， AA ADPKD患者SCT和G6PD缺乏症的频率将为 测定并与当地AA人群进行比较。这些条件 将与它们与肾脏疾病的共同隔离相关 用卡方分析进行级数分析。最后，我们将确定 DAPKD病基因在我们AA队列中的频率 每个队列内的连锁分析。 再生障碍性ADPKD患者的基因分布及其可能的相关性研究 病态的遗传风险因素将提供更好的理解 这种疾病的分子基础，并将在临床上有用的风险 分层和遗传咨询。本提案旨在作为 先导研究。我们期望这些研究可以扩展到比较ADPKD 阿拉巴马州高加索人对阵戒酒协会。此外，几名库尔德工人党调查人员 都表示有兴趣制定一项多中心研究来评估 再生障碍性贫血患者应用ADPKD的国家经验。

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in the United States, affecting 1 in 400 to 1 in 1,000 individuals. The clinical and genetic factors associated with disease progression have been well-defined in the Caucasian population but there is a paucity of data for other racial groups, including African- Americans (AA). There is anecdotal evidence which suggests that glucose-6- phosphate dehydrogenase (G6PD) deficiency and sickle cell trait (SCT) are negative prognostic factors in AA ADPKD patients. At least three independent loci cause ADPKD in Caucasian populations. The genetic defect(s) in the AA population has not been established nor has the frequency distribution of these ADPKD loci. This project will characterize the natural history of ADPKD in the AA population of Alabama to determine whether specific clinical and genetic factors are associated with progression of renal disease. We will define the frequency of dichotomous variables previously associated with progressive renal dysfunction in Caucasians (including gender, hypertension, hematuria, nephrolithiasis, proteinuria, cyst rupture, and UTI) in AA ADPKD patients. Frequency of these variables will be compared in age-matched AA individuals with and without ESRD and correlated with age of onset of ESRD. Also, the frequency of SCT and G6PD deficiency in AA ADPKD patients will be determied and compared with the local AA population. These conditions will be correlated with their co-segregation with renal disease progression using chi-squared analysis. Finally, we will determine the DAPKD disease gene frequency in our AA cohort by performing genetic linkage analysis within each cohort. Knowledge of the gene distribution in AA ADPKD patients and putative co- morbid genetic risk factors will provide a better understanding of the molecular basis of this disorder and will be clinically useful in risk stratification and genetic counseling. This proposal is designed as a pilot study. We anticipate these studies can be extended to compare ADPKD in Alabama Caucasians versus AA. In addition, several PKD investigators have expressed interest in formulating a multi-center study to evaluate the national experience with ADPKD in AA patients.