Association of genetic polymorphisms of ET-1 related genes with progression of target organ damages in hypertensive patients

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Endothelin-1 (ET-1) system plays a crucial role in vasoconstriction and is a promising target for the genetic analysis of hypertension and its complications. Blood pressure (BP) variations, especially non-dipping patterns during sleep, are known to be associated with progression of cardiovascular target organ damages in hypertensive patients. In this study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in ET-1 related genes and circadian variation of BP in Japanese hypertensives. We genotyped 19 SNPs in ET-1 related genes of 334 essential hypertensive subjects and found that SNPs in ECE2 (G28372A and C28586T) were significantly associated with the non-dipping pattern of BP. We also examined the association between SNPs of ET-1 related genes and prevalence of chronic kidney disease (CKD) complication in Japanese hypertensives. We observed significant association between the SNPs in EDNRA (T54204C, G54240A and A57938G) and CKD in Japanese patients with essential hypertension. Taken together, our results revealed the ET-1 system as an important system involved in target organ damages in essential hypertension in Japanese.