Association of the calcium-sensing receptor gene with blood pressure and urinary calcium in african-americans

Abstract

Context: Calcium binding to the Ca-sensing receptor (CASR) expressed in thick ascending limb inhibits the Na,K,2CI cotransporter, which decreases sodium reabsorption and secondarily decreases Ca reab-sorption. CASR gene variants could influence blood pressure (BP) by affecting Na retention.Objective: The objective of the study was to determine whether variations in CASR associated with BP in African-Americans, an ethnic group at high risk for hypertension.Design: Population-and family-based association studies of single-nucleotide polymorphisms (SNPs) in CASR with BP measured over the age range 5.6-25 yr (14 biannual visits per subject on average) were carried out. In a cross-sectional study where urinary Ca excretion had been measured, Ca excretion was used as an additional phenotype of CASR influence on Na,K,2CI cotransporter activity.Participants: Subjects were normotensive. In the longitudinal study, there were 223 subjects (mean age 14 yr) and 123 families (one or both parents provided a DNA sample); in the cross-sectional study, there were 106 subjects (mean age 23 yr) and 88 families.Results: Three SNPs in linkage disequilibrium associated with systolic BP at P < 0.005 (the significance threshold corrected for multiple comparisons) in the population-based longitudinal study. In the cross-sectional study, SNPs contained in the same linkage disequilibrium block associated with urinary Ca excretion in both population- and family-based association tudies.Conclusion: The findings suggestthat in African-Americans, functional heterogeneity of the CASR.