The long term goal of the proposed study is to gain insight into the genetic basis of essential hypertension. Hyper-tension and its effects are a major health problem in the United States, and are particularly severe within the African-American community. Because of the disproportionately high incidence of hypertension in African-Americans, this project will analyze people of African descent exclusively. By choosing this highly afflicted ethnic group problems of genetic heterogeneity will be minimized and the underlying genetic factors should be easier to dissect. Affected sib-pairs and families will initially be recruited from Nashville, TN and rural and urban Ghana, West Africa. The incidence of hypertension in these populations varies dramatically, with US Blacks being highest, followed by urban and the rural Ghanaians. Comparisons of these populations will be important in assessing the genetic vs. environmental contribution to hyper-tension. The approach to be used in this study is to ascertain sib-pairs in which one or both have hypertension and determine the contribution of specific alleles to hypertension, using an allele sharing methodology. Initially three candidate loci, angiotensin I converting enzyme, angiotensinogen, and renin, and closely linked markers will be analyzed. All of these loci are in the same physiological pathway and have been hypothesized to be important in the control of blood pressure. Analysis of DNA segments obtained by PCR ampli-fication will be used to detect specific allele states in the different individuals. Following this a systematic genome search will be done to identify other genomic regions that contribute to the high blood pressure phenotype. This design will detect any associations with these genes and hypertension. As new data become available, other candidate genes will also be analyzed in these subjects.
| Williams, Scott M; Ritchie, Marylyn D; Phillips 3rd, John A et al. (2004) Multilocus analysis of hypertension: a hierarchical approach. Hum Hered 57:28-38 |
| Moore, Jason H; Williams, Scott M (2002) New strategies for identifying gene-gene interactions in hypertension. Ann Med 34:88-95 |
| Tarumi, T; Martincic, D; Whitlock, J A et al. (2000) Conserved worldwide linkage disequilibrium in the human factor XI gene. Genomics 70:269-72 |
