No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension.
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.
Benjafield
Adam V
AV
Basic Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.
Wang
William Y S
WY
Morris
Brian J
BJ
D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D001315:Australia / Q000453:epidemiology; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D002268:Carboxypeptidases / Q000235:genetics*; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012737:Sex Factors; D013223:Statistics as Topic; D013599:Systole / Q000235:genetics
D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2