Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population

Chia Ti Tsai, Juey Jen Hwang, Cho Kai Wu, Jen Kuang Lee, Chuen Den Tseng, Yi Chih Wang, Kuan Lih Hsu, Ling Ping Lai, Jiunn Lee Lin, Fu Tien Chiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions. Methods: A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between ACE and AT1R genes. Results: We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16-2.29]; P= 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype. Conclusions: The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalClinica Chimica Acta
Volume412
Issue number7-8
DOIs
Publication statusPublished - Mar 18 2011
Externally publishedYes

Fingerprint

Angiotensins
Renin-Angiotensin System
Renin
Coronary Artery Disease
Genes
Haplotypes
Population
Angiotensinogen
Peptidyl-Dipeptidase A
Polymorphism
Odds Ratio
Angiotensin I
Angiotensin Receptors
Cardiac Catheterization
Angiotensin II

Keywords

  • Coronary artery disease
  • Gene-gene interaction
  • Genetics
  • Haplotype
  • Multilocus
  • Regression

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population. / Tsai, Chia Ti; Hwang, Juey Jen; Wu, Cho Kai; Lee, Jen Kuang; Tseng, Chuen Den; Wang, Yi Chih; Hsu, Kuan Lih; Lai, Ling Ping; Lin, Jiunn Lee; Chiang, Fu Tien.

In: Clinica Chimica Acta, Vol. 412, No. 7-8, 18.03.2011, p. 619-624.

Research output: Contribution to journalArticle

Tsai, Chia Ti ; Hwang, Juey Jen ; Wu, Cho Kai ; Lee, Jen Kuang ; Tseng, Chuen Den ; Wang, Yi Chih ; Hsu, Kuan Lih ; Lai, Ling Ping ; Lin, Jiunn Lee ; Chiang, Fu Tien. / Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population. In: Clinica Chimica Acta. 2011 ; Vol. 412, No. 7-8. pp. 619-624.
@article{bb3d163486ac4c61b61529ed910abc63,
title = "Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population",
abstract = "Background: Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions. Methods: A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between ACE and AT1R genes. Results: We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16-2.29]; P= 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype. Conclusions: The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.",
keywords = "Coronary artery disease, Gene-gene interaction, Genetics, Haplotype, Multilocus, Regression",
author = "Tsai, {Chia Ti} and Hwang, {Juey Jen} and Wu, {Cho Kai} and Lee, {Jen Kuang} and Tseng, {Chuen Den} and Wang, {Yi Chih} and Hsu, {Kuan Lih} and Lai, {Ling Ping} and Lin, {Jiunn Lee} and Chiang, {Fu Tien}",
year = "2011",
month = "3",
day = "18",
doi = "10.1016/j.cca.2010.12.017",
language = "English",
volume = "412",
pages = "619--624",
journal = "Clinica Chimica Acta",
issn = "0009-8981",
publisher = "Elsevier",
number = "7-8",

}

TY - JOUR

T1 - Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population

AU - Tsai, Chia Ti

AU - Hwang, Juey Jen

AU - Wu, Cho Kai

AU - Lee, Jen Kuang

AU - Tseng, Chuen Den

AU - Wang, Yi Chih

AU - Hsu, Kuan Lih

AU - Lai, Ling Ping

AU - Lin, Jiunn Lee

AU - Chiang, Fu Tien

PY - 2011/3/18

Y1 - 2011/3/18

N2 - Background: Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions. Methods: A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between ACE and AT1R genes. Results: We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16-2.29]; P= 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype. Conclusions: The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.

AB - Background: Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions. Methods: A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between ACE and AT1R genes. Results: We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16-2.29]; P= 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype. Conclusions: The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.

KW - Coronary artery disease

KW - Gene-gene interaction

KW - Genetics

KW - Haplotype

KW - Multilocus

KW - Regression

UR - http://www.scopus.com/inward/record.url?scp=79551477874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551477874&partnerID=8YFLogxK

U2 - 10.1016/j.cca.2010.12.017

DO - 10.1016/j.cca.2010.12.017

M3 - Article

VL - 412

SP - 619

EP - 624

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

SN - 0009-8981

IS - 7-8

ER -