Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension

Abstract

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1 is thought to play an important role in the development of atherosclerosis, it remains unclear whether polymorphisms of ET-1 family genes, including the ET-1 gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2 (ECE1 and ECE2 ), are associated with the progression of atherosclerosis. We investigated the relationship between 11 single nucleotide polymorphisms (SNPs) of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four in ECE1 and one in ECE2 ) and atherosclerotic changes assessed using pulse wave velocity (PWV) and carotid ultrasonography in 630 patients with essential hypertension (EHT). In male subjects, we found significant differences in brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after Bonferroni correction. Also in male subjects, there were significant differences in mean intima-media thickness (IMT) in additive and recessive models in EDNRA-rs5333 after Bonferroni correction. We found no significant correlation between any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female subjects. Furthermore, after multiple logistic regression analysis, only EDNRB-rs5351 indicated as an independent risk of atherosclerosis in male hypertensive subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients.

New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing

“…In combination with rs10757274 the risk for developing CHD almost doubles 28 . In addition, the Iceman's genome harbours endothelin receptor type B heterozygote variant rs5351, which independently increases the risk for atherosclerosis in men 29 . In addition, we found SNPs in three genes that have been associated with CHD, namely VDR, TBX5 and BDKRB1.…”

Assiciations of Hypertension and Its Complications with Variations in the Xanthine Dehydrogenase Gene

“…IMT above 1.0 mm in either the left or right common carotid artery defined with the presence of an atherosclerotic lesion. We also assessed arterial stiffness using brachial-ankle-pulse wave velocity (ba-PWV) measured by form ABI (Omron Health Care, Kyoto, Japan) as described in a previous report (32). Estimated creatinine clearance (Ccr) determined with the Cockcroft-Gault formula (33) was used for the evaluation of CKD.…”

Polymorphisms in the Endothelin-1 and Endothelin A Receptor Genes and Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

“…The SNPs in EDN1 and EDNRA genes are associated with susceptibility and prognosis of some diseases, including glaucoma, heart failure, dilated cardiomyopathy, diabetic retinopathy, and atherosclerosis (18)(19)(20)(21)(22)(23). It remains unclear, however, whether gene polymorphisms of the EDN1 and EDNRA are associated with the prognosis of NPC patients.…”

“…The specific polymorphic loci examined included EDN1 G8002A (rs2071942), EDN1 Lys198Asn (rs57072783), EDN1T-1370G (rs1800541), EDNRA H323H (rs5333), EDNRA Cþ70G (rs5335), EDNRA Cþ1222T (rs5343), and EDNRA G-231A (rs1801708). These SNPs were selected using the following criteria: associated with susceptibility and prognosis of other diseases (18)(19)(20)(21)(22)(23) and adequate frequency in Asian populations to enable evaluation. DNA was extracted from peripheral lymphocytes using the QIAamp DNA Blood Midi Kit (QIAGEN).…”