Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension.
In a study of the genetic basis of essential hypertension (HT), we tested four variants in three candidate genes not previously investigated in HT. These encoded the endothelin receptor type A (EDNRA), which transduces most of the vasoconstrictive properties of endothelin-1, protein kinase lysine deficient 4 (WNK4) whose gene resides in a HT linkage region on chromosome 17, and FK506-binding protein 1B (FKBP1B), which can reduce blood pressure by increasing nitric oxide. The variants were: for EDNRA, a G-->A in the 5'-UTR and C-->T in exon 8; for WNK4, a tetranucleotide repeat in intron 10; and for FKBP1B, a T-->C in exon 4. Subjects were Anglo-Celtic white Australians and included 155 HTs with two HT parents and 245 normotensives (NTs) whose parents were both NT. For EDNRA, we found a weak association of the exon 8 variant with HT (p = 0.019) and association of the 5'-UTR variant with elevation in systolic and diastolic blood pressure (BP) (p = 0.038 and 0.0031, respectively). The WNK4 intron 10 variant and the FKP1B exon 4 variant showed no association with HT, but tracking with BP was seen for the latter (p = 0.015 and 0.0011 for systolic and diastolic BP, respectively). Our study thus suggests possible involvement of EDNRA in essential HT.
Benjafield
A V
AV
Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute of Biomedical Research, The University of Sydney, Sydney, NSW, Australia.
Katyk
K
K
Morris
B J
BJ
D020121:5' Untranslated Regions / Q000235:genetics; D000368:Aged; D019943:Amino Acid Substitution; D001794:Blood Pressure; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017466:Receptors, Endothelin / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*
D020121:5' Untranslated Regions; D017466:Receptors, Endothelin; D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B