ADPKD--NATURAL HISTORY AND GENE DISTRIBUTION IN AFRICAN AMERICANS

常染色体显性遗传性多囊肾病（ADPKD）是最常见的 在美国，遗传性肾病的发病率为1/400至1/400。 一千个人。 与此相关的临床和遗传因素 疾病进展在高加索人群中已得到明确定义， 其他种族群体的数据很少，包括非洲人- 美国人（AA）。有证据表明葡萄糖-6- 磷酸脱氢酶（G6PD）缺乏和镰状细胞性状（SCT）是 AA ADPKD患者的不良预后因素。 至少三 高加索人群中ADPKD的独立基因座。 遗传 AA人群中的缺陷尚未确定， 这些ADPKD基因座的频率分布。该项目将以 亚拉巴马AA人群中ADPKD的自然史，以确定 特定的临床和遗传因素是否与 肾脏疾病的进展。 我们将定义二分的频率 既往与肾功能不全相关的变量 白人（包括性别、高血压、血尿、肾结石、 蛋白尿、囊肿破裂和UTI）。 频率 这些变量将在年龄匹配的AA个体中进行比较， 无终末期肾病，与终末期肾病发病年龄相关。 还 AA ADPKD患者中SCT和G6PD缺陷的频率将 并与当地AA人群进行比较。 这些条件 将与其与肾脏疾病的共分离相关 使用卡方分析的进展。 最后，我们将确定 通过遗传学分析，我们的AA队列中DAPKD疾病基因频率 每个队列中的连锁分析。 了解AA ADPKD患者的基因分布和假定的共- 病态遗传风险因素将提供一个更好的理解， 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。 该提案旨在作为一项 试点研究。 我们预计这些研究可以扩展到比较ADPKD 在亚拉巴马白人对嗜酒者互诫协会中。 此外，一些PKD调查人员 表示有兴趣制定一项多中心研究， AA患者中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.