Association of the calcium-sensing receptor gene with blood pressure and urinary calcium in African-Americans.
BACKGROUND
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.


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.


METHODS
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.


METHODS
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 studies.


CONCLUSIONS
The findings suggest that in African-Americans, functional heterogeneity of the CASR in thick ascending limb may influence BP.
Jung
Jeesun
J
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Foroud
Tatiana M
TM
Eckert
George J
GJ
Flury-Wetherill
Leah
L
Edenberg
Howard J
HJ
Xuei
Xiaoling
X
Zaidi
Syed-Adeel
SA
Pratt
J Howard
JH
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001794:Blood Pressure; D002118:Calcium / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D055815:Young Adult
D044169:Receptors, Calcium-Sensing; D002118:Calcium