title: Fine-mapping angiotensin-converting enzyme gene: separate QTLs identified for hypertension and for ACE activity.
abstract: Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(-16) to <10(-33)). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3'UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.forename: Ruey-Yun
authors.initials: RY
authors.lastname: Wang
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Yuh-Shiun
authors.initials: YS
authors.lastname: Jong
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.forename: Chih-Sen
authors.initials: CS
authors.lastname: Kang
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Chen
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
mesh_terms: D000328:Adult; D017668:Age of Onset; D005091:Exons; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D013624:Taiwan / Q000453:epidemiology
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A