ADPKD--NATURAL HISTORY AND GENE DISTRIBUTION IN AFRICAN AMERICANS

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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.