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

Journal of Human Hypertension volume 21, pages 883–892 (2007)Cite this article

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.

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Acknowledgements

This study was supported by the Programme for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) of Japan, and a Grant-in Aid and a Research Grant for Cardiovascular Diseases (16C-1) from the Japanese Ministry of Health, Labour, and Welfare of Japan. We thank Chihiro Tanaka and Mariko Banno for their excellent technical assistance and to Erumu Hayase and Chikako Tokudome for their administrative help.

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Authors and Affiliations

  1. Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka, Japan

    H Yasuda, K Kamide, S Takiuchi, T Matayoshi, J Yang, Y Miwa, M Yoshii, T Horio, F Yoshihara, S Nakamura, H Nakahama & Y Kawano

  2. Research Institute, National Cardiovascular Center, Suita, Osaka, Japan

    H Hanada, A Kada, J Yang & T Miyata

  3. Department of Cardiovascular, Respiratory and Metabolic Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan

    C Tei

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  1. H Yasuda
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Correspondence to K Kamide.

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Yasuda, H., Kamide, K., Takiuchi, S. et al. Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension. J Hum Hypertens 21, 883–892 (2007). https://doi.org/10.1038/sj.jhh.1002234

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  • DOI: https://doi.org/10.1038/sj.jhh.1002234

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