No association of Angiotensin-Converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension(*)

Benjafield, Adam V.; Wang, William Y.S.; Morris, Brian J.

Recent intriguing findings from genetic linkage, knockout, and physiologic studies in mice and rats led us to conduct the first investigation of the novel angiotensin-converting enzyme 2 gene (ACE2) in human hypertension (HT). We genotyped four single nucleotide polymorphisms (SNP) (A⇒G at nucleotide 1075 in intron 1, G⇒A at nucleotide 8790 in intron 3, C⇒G at nucleotide 28330 in intron 11, and G⇒C at nucleotide 36787 in intron 16) in HT (n = 152) and normotensive (NT, n = 193) groups having inherently high biological power (>80%) due to our inclusion only of subjects whose parents had the same BP status as themselves. The SNPs were in linkage disequilibrium (D′ = 54% to 100%, P = .05 to 0.0001). Because ACE2 is on the X chromosome, data for each sex were analyzed separately. Minor allele frequencies in HT versus NT were as follows: for the intron 1 variant 0.21 versus 0.17 in female subjects (P = .31) and 0.25 versus 0.29 in male subjects (P = .60); intron 3 variant 0.22 versus 0.18 in female subjects (P = .35) and 0.15 versus 0.20 in male subjects (P = .47); intron 11 variant 0.39 versus 0.46 in male subjects (P = 0.17) and 0.31 versus 0.30 in male subjects (P = .96); intron 16 variant 0.20 versus 0.19 in female subjects (P = .72) and 0.17 versus 0.17 in male subjects (P = .95). Haplotype analysis was also negative. These data provide little support for ACE2 in genetic predisposition to HT. Am J Hypertens 2004;17:624–628 © 2004 American Journal of Hypertension, Ltd.