Genome-Wide Scan for Quantitative ACE Activity in Taiwan Young-Onset Hypertension Study

Wang, Ruey Yun; Chung, Chia Min; Fann, Cathy S.J.; Yang, Hsin-Chou; Chen, Jaw Wen; Jong, Yuh Shiun; Jou, Yuh–Shan; Lo, Huey‐Ming; Ho, Feng Ming; Kang, Chih Sen; Chen, Chien‐Chung; Chang, Huan Cheng; Shyue, Song Kun; Pan, Wen Harn

doi:10.1159/000108940

Cited by 8 publications

(5 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By using the Han Chinese SNP database with SNPbrowser software (Applied Biosystems), we selected 41 SNPs (distributed over ACE and another 11 genes) based on Assay-on-Demand (Applied Biosystems) with a minor allele frequency (MAF) of 0.2 or more (data not shown) within and around the ACE gene and within 1 cM of the highest two-point and multipoint LOD scores from the results of our previous study [17]. Association tests showed that only one (rs4353) out of six SNPs (rs4293, rs4295, rs4353, rs4575595, rs11868324, and rs4267385) located in the ACE gene was statistically significant after Bonferroni correction.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, following up on our previous genomewide scan study [17] we set out to map QTLs for serum ACE activity and to examine their effects on hypertension by analysis of variance approach and measured haplotype analysis. We employed a two-stage approach using, first, data from a Taiwan young-onset hypertension family study and, second, information from an Academia Sinica multi-center study of young-onset hypertension.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

et al. 2013

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…We excluded angiotensin I-converting enzyme and lipoprotein lipase genes that have been extensively studied in our group. 14,17,18 We also excluded angiotensin II receptor (AGTR2) gene that showed no association in our recent pooling case-control study. In total, we selected 36 candidate genes among which AGT, AGTR1, CYP11B2, GNB3, NOS3, and ADD1 have ≥20 papers recorded.…”

Section: Methodsmentioning

confidence: 99%

A Two-Stage Matched Case–Control Study on Multiple Hypertensive Candidate Genes in Han Chinese

Kuo¹,

Kang²,

Chen³

et al. 2012

American Journal of Hypertension

Self Cite

View full text Add to dashboard Cite

SNP rs2301339 is perfectly linked in linkage disequilibrium (LD) with C825T (rs5443) which has been associated with hypertension in Caucasian, but inconsistent in Asian populations. However, we found that in our sample this SNP has an opposite effect with the previous findings. In summary, this study identified one novel SNP in GNB3 and one novel SNP in INSR that are strongly associated with young-onset hypertension. Due to relatively small sample size, the results should still be interpreted with caution and need to be replicated in other studies.

show abstract

“…Although clinical profile and candidate gene studies have sketched a blueprint for genetic susceptibility in YOH in the Han Chinese population [12]–[15], meticulous dissection of YOH by a systematic genome-wide association study has not been performed. This study aims to identify YOH susceptibility genes for the Han Chinese population based on a two-stage study design consisting of a genome-wide association study (GWAS) and a confirmatory association study (CMAS).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Yang

et al. 2009

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

show abstract

Genome-Wide Scan for Quantitative ACE Activity in Taiwan Young-Onset Hypertension Study

Cited by 8 publications

References 72 publications

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

A Two-Stage Matched Case–Control Study on Multiple Hypertensive Candidate Genes in Han Chinese

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Contact Info

Product

Resources

About