Association of the Calcium-Sensing Receptor Gene with Blood Pressure and Urinary Calcium in African-Americans

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 03/2009; 94(3):1042-8. DOI: 10.1210/jc.2008-1861
Source: PubMed


Calcium binding to the Ca-sensing receptor (CASR) expressed in thick ascending limb inhibits the Na,K,2Cl cotransporter, which decreases sodium reabsorption and secondarily decreases Ca reabsorption. CASR gene variants could influence blood pressure (BP) by affecting Na retention.
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.
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,2Cl cotransporter activity.
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.
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 studies.
The findings suggest that in African-Americans, functional heterogeneity of the CASR in thick ascending limb may influence BP.

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    • "Polymorphism in human CaR gene is associated with increased frequency of coronary heart disease, myocardial infarction and cardiovascular death (März et al., 2007). Moreover , a recent study showed that common variations in the CaR are associated with blood pressure in young African Americans (Jung et al., 2009), suggesting the involvement of the CaR in the control of blood pressure. Although the authors suggest that the effect on blood pressure was through the CaR gene variants effect on sodium retention, further study is necessary. "
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