Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension

Abstract

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.

Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study

“…Stevens and Brown 16 found no association between the rs5333 (H323H) polymorphism in a study of 100 cases and 100 controls. Benjafield et al 17 studied 155 hypertensives and 245 controls for the rs1801708 (G-231A) polymorphism; they also studied a C þ 1363T SNP which is located downstream of rs5335 (C þ 70G) in the untranslated region of the eighth exon. They found no association between the G-231A SNP and hypertension, but a borderline significant association (P ¼ 0.019) between the C allele of the C þ 1363T SNP and hypertension.…”

Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population

“…A polymorphism in WNK4 (base1156666G>A) has been reported to be associated with hypertension in a Caucasian population (Erlich et al 2003) with a discrepancy in other studies (Benjafield et al 2003;Speirs and Morris 2004). We hypothesized that the genetic polymorphisms in TSC, WNK1, and WNK4 may involve changes in BP level.…”

WNK4 Intron 10 Polymorphism Is Not Associated With Hypertension

“…The present finding adds, moreover, to our previous negative finding for another variant in intron 10 of WNK4. 22 Erlich et al noted the association with hypertension in white, but not in black, hypertensives. 15 Whereas we found that the frequency of the minor allele was 0.10 in each group, they found frequencies of 0.13 in 165 hypertensives and 0.07 in 91 normotensives.…”