A genome scan for renal function among hypertensives: The HyperGEN study

Decreased renal function is often a complication of hypertension. Although it has been suggested that the response of the kidney to hypertension has a n underlying genetic component, there is limited information suggesting tha t specific genetic regions or candidate genes contribute to the variability in creatinine clearance, a commonly used measure of kidney function. As pa rt of the Hypertension Genetic Epidemiology Network (HyperGEN) study, creat inine clearance measurements were assessed in a large biracial sample of hy pertensive siblings (466 African American subjects and 634 white subjects i n 215 and 265 sibships, respectively). All participants were hypertensive b efore the age of 60 years, and the mean age of the siblings was 52 years am ong the African American subjects and 61 years among the white subjects. Tw o residual models were created for creatinine clearance: a minimally adjust ed model (which included age and age(2)) and a fully adjusted model (which included age, age(2), lean body mass, pulse rate, pulse pressure, hormone-r eplacement therapy, educational status, and physical activity). Standardize d residuals were calculated separately for men and women in both racial gro ups. The heritability of the residual creatinine clearance was 17% and 18% among the African American and white subjects, respectively. We conducted m ultipoint variance components linkage analysis using GENEHUNTER2 and 387 an onymous markers (Cooperative Human Linkage Center screening set 8). The bes t evidence for linkage in African American subjects was found on chromosome 3 (LOD = 3.61 at 214.6 cM, 3q27) with the fully adjusted model, and the be st evidence in white subjects was found on chromosome 3 (LOD = 3.36 at 115. 1 cM) with the minimally adjusted model. Positional candidate genes that ar e contained in and around the region on chromosome 3 (214.6 cM) that may co ntribute to renal function include enoyl-CoA hydratase/3-hydroxyacyl-CoA de hydrogenase (EHHADH) and apo lipoprotein D (ApoD). These findings suggest t here may be genetic regions related to the variability of creatinine cleara nce among hypertensive individuals.