Open AccessFine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity
Author(s) -
Chia Min Chung,
Ruey Yun Wang,
Cathy S.J. Fann,
Jaw Wen Chen,
Yuh Shiun Jong,
Yuh–Shan Jou,
Hsin-Chou Yang,
Chih Sen Kang,
ChienChung Chen,
Huan Cheng Chang,
Wen Harn Pan
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0056119
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , haplotype , genetics , angiotensin converting enzyme , biology , snp , gene , medicine , allele , endocrinology , genotype , blood pressure
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.