Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension. 1752 6

Endothelin-1 (EDN1), a 21-amino acid peptide, is a potent vasoconstrictor with various pharmacological responses. EDN1 is synthesized from a 212-amino acid precursor protein, preproEDN1, through multiple proteolytic steps. Endothelin-converting enzyme (ECE) cleaves a Trp73-Val74 peptide bond in big-EDN1 to give rise to mature EDN1. In this study, we examined the possible association of genetic variations in ECE1 with hypertension in a general Japanese population and searched for missense mutations in and around the EDN1 polypeptide. We genotyped 5 single nucleotide polymorphisms (SNPs) in the ECE1 gene in 1,873 individuals from a general Japanese population and identified one SNP associated with hypertension in women (rs212528: TT vs. TC+CC: odds ratio=1.40; 95% confidence intervals: 1.04-1.89; p=0.026), after adjusting for confounding factors. The systolic blood pressure in women with the CC genotype was 6.44 mmHg higher than that in those with the TT genotype (p=0.007), after adjusting for the same factors. Next, to identify the missense mutations that may influence the biological activity of EDN1, we sequenced the genomic region that encodes EDN1 in 942 Japanese hypertensive patients. We identified a novel missense mutation, G36R, in one hypertensive patient, but no mutations were observed in EDN1. A gene polymorphism in EDN1, Lys198Asn, has been reported to be associated with hypertension in obese subjects. Taken together, these findings reveal that the EDN-ECE pathway is an important system involved in essential hypertension in Japanese.
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PMID:Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives. 1766 54