title: Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension.
abstract: Abnormal renal reabsorption of sodium (Na(+)) is likely to play a role in the pathogenesis of salt-sensitivity. In the kidney, chloride channels CLC-Ka (gene CLCNKA) and CLC-Kb (gene CLCNKB) and their subunit Barttin (gene BSND) have important effects on the control of Na(+) and water homeostasis. We investigated if single nucleotide polymorphisms (SNPs) or haplotypes within CLCNKA, CLCNKB and BSND loci affect salt-sensitivity in hypertensive subjects. Associations between blood pressure (BP) change after Na(+)-load and 15 SNPs spanning the length of CLCNKA and CLCNKB and six SNPs spanning the length of BSND were studied in 314 never treated essential hypertensives who underwent an i.v. infusion of saline (300 mm NaCl in 2 l H(2)O in 120 min). Four SNPs were significantly associated with BP change after Na-load. Rs848307 (P = 0.0026) and rs1739843 (P = 0.0023) map upstream the 5' of CLCNKA. Non-coding Rs1010069 (P = 0.0006) and non-synonymous rs1805152 (Thr447Ala; P = 0.0078) map within CLCNKA. Moreover, basal plasma renin activity and heart rate (measured before Na-load) were significantly lower in patients carrying the alleles associated with the larger mean BP increase after Na-load, indicating that such alleles are associated with chronic volume expansion. This study supports the candidacy of CLCNKA as a new susceptibility gene for salt-sensitivity.
authors.affiliation: Department of Sciences and Biomedical Technologies, University of Milan, Via Fantoli 16/15, 20090 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barlassina
authors.forename: Chiara
authors.initials: C
authors.lastname: Dal Fiume
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.forename: Guia
authors.initials: G
authors.lastname: Guffanti
authors.forename: Antonella
authors.initials: A
authors.lastname: Ruello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
mesh_terms: D000368:Aged; D000483:Alleles; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012964:Sodium / Q000378:metabolism
chemical_list: C489932:CLCNKA protein, human; D018118:Chloride Channels; D012964:Sodium