A propensity score-based case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure

Cho Kai Wu, Jing Ling Luo, Xue Ming Wu, Chia Ti Tsai, Jou Wei Lin, Juey Jen Hwang, Jiunn Lee Lin, Chuen Den Tseng, Fu Tien Chiang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Angiotensin II plays an important role in diastolic heart failure (DHF). However, genetic studies of DHF are scarce in the literature. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a propensity score-based case-control study to prove this hypothesis. A total of 666 subjects (285 diagnosed with DHF confirmed by echocardiography and 381 without diastolic dysfunction) were recruited. Genotyped were: the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; the T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene. Propensity scores (PS) were used to find patients with and without DHF with equalized characteristics. We also assembled another set of PS matched groups for all characteristics except left ventricular mass (LVM) to detect the genetic association with DHF through the effect of left ventricular hypertrophy. PS matched 210 patients with DHF to 210 without. In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype (OR = 1.30, 95% CI = 1.13-1.49, permuted P = 0.003) and the AT1R 1166 CC genotype (OR = 2.61, 95% CI = 1.52-4.45, permuted P < 0.001). Significant gene-gene interaction between the two genes was also detected. However, the ACE gene effect was diminished if LVM was not controlled in the propensity scores. We concluded that genetic variants in the RAS genes may determine individual risk to develop DHF through different pathways. Concomitant presence of ACE DD and AT1R 1166 CC genotypes synergistically increased the predisposition to DHF.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalAtherosclerosis
Volume205
Issue number2
DOIs
Publication statusPublished - Aug 1 2009
Externally publishedYes

Fingerprint

Diastolic Heart Failure
Propensity Score
Renin-Angiotensin System
Case-Control Studies
Genes
Peptidyl-Dipeptidase A
Odds Ratio
Genotype
Angiotensin I
Angiotensinogen
Angiotensin Receptors
Insertional Mutagenesis
Gene Deletion
Left Ventricular Hypertrophy
Angiotensin II
Echocardiography
Research Design

Keywords

  • Angiotensin-converting enzyme
  • Diastolic heart failure
  • Genetics
  • Polymorphism
  • Propensity score

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A propensity score-based case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure. / Wu, Cho Kai; Luo, Jing Ling; Wu, Xue Ming; Tsai, Chia Ti; Lin, Jou Wei; Hwang, Juey Jen; Lin, Jiunn Lee; Tseng, Chuen Den; Chiang, Fu Tien.

In: Atherosclerosis, Vol. 205, No. 2, 01.08.2009, p. 497-502.

Research output: Contribution to journalArticle

Wu, Cho Kai ; Luo, Jing Ling ; Wu, Xue Ming ; Tsai, Chia Ti ; Lin, Jou Wei ; Hwang, Juey Jen ; Lin, Jiunn Lee ; Tseng, Chuen Den ; Chiang, Fu Tien. / A propensity score-based case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure. In: Atherosclerosis. 2009 ; Vol. 205, No. 2. pp. 497-502.
@article{b6033707712e4885adee1c56cc251b53,
title = "A propensity score-based case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure",
abstract = "Angiotensin II plays an important role in diastolic heart failure (DHF). However, genetic studies of DHF are scarce in the literature. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a propensity score-based case-control study to prove this hypothesis. A total of 666 subjects (285 diagnosed with DHF confirmed by echocardiography and 381 without diastolic dysfunction) were recruited. Genotyped were: the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; the T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene. Propensity scores (PS) were used to find patients with and without DHF with equalized characteristics. We also assembled another set of PS matched groups for all characteristics except left ventricular mass (LVM) to detect the genetic association with DHF through the effect of left ventricular hypertrophy. PS matched 210 patients with DHF to 210 without. In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype (OR = 1.30, 95{\%} CI = 1.13-1.49, permuted P = 0.003) and the AT1R 1166 CC genotype (OR = 2.61, 95{\%} CI = 1.52-4.45, permuted P < 0.001). Significant gene-gene interaction between the two genes was also detected. However, the ACE gene effect was diminished if LVM was not controlled in the propensity scores. We concluded that genetic variants in the RAS genes may determine individual risk to develop DHF through different pathways. Concomitant presence of ACE DD and AT1R 1166 CC genotypes synergistically increased the predisposition to DHF.",
keywords = "Angiotensin-converting enzyme, Diastolic heart failure, Genetics, Polymorphism, Propensity score",
author = "Wu, {Cho Kai} and Luo, {Jing Ling} and Wu, {Xue Ming} and Tsai, {Chia Ti} and Lin, {Jou Wei} and Hwang, {Juey Jen} and Lin, {Jiunn Lee} and Tseng, {Chuen Den} and Chiang, {Fu Tien}",
year = "2009",
month = "8",
day = "1",
doi = "10.1016/j.atherosclerosis.2008.12.033",
language = "English",
volume = "205",
pages = "497--502",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - A propensity score-based case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure

AU - Wu, Cho Kai

AU - Luo, Jing Ling

AU - Wu, Xue Ming

AU - Tsai, Chia Ti

AU - Lin, Jou Wei

AU - Hwang, Juey Jen

AU - Lin, Jiunn Lee

AU - Tseng, Chuen Den

AU - Chiang, Fu Tien

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Angiotensin II plays an important role in diastolic heart failure (DHF). However, genetic studies of DHF are scarce in the literature. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a propensity score-based case-control study to prove this hypothesis. A total of 666 subjects (285 diagnosed with DHF confirmed by echocardiography and 381 without diastolic dysfunction) were recruited. Genotyped were: the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; the T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene. Propensity scores (PS) were used to find patients with and without DHF with equalized characteristics. We also assembled another set of PS matched groups for all characteristics except left ventricular mass (LVM) to detect the genetic association with DHF through the effect of left ventricular hypertrophy. PS matched 210 patients with DHF to 210 without. In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype (OR = 1.30, 95% CI = 1.13-1.49, permuted P = 0.003) and the AT1R 1166 CC genotype (OR = 2.61, 95% CI = 1.52-4.45, permuted P < 0.001). Significant gene-gene interaction between the two genes was also detected. However, the ACE gene effect was diminished if LVM was not controlled in the propensity scores. We concluded that genetic variants in the RAS genes may determine individual risk to develop DHF through different pathways. Concomitant presence of ACE DD and AT1R 1166 CC genotypes synergistically increased the predisposition to DHF.

AB - Angiotensin II plays an important role in diastolic heart failure (DHF). However, genetic studies of DHF are scarce in the literature. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a propensity score-based case-control study to prove this hypothesis. A total of 666 subjects (285 diagnosed with DHF confirmed by echocardiography and 381 without diastolic dysfunction) were recruited. Genotyped were: the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; the T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene. Propensity scores (PS) were used to find patients with and without DHF with equalized characteristics. We also assembled another set of PS matched groups for all characteristics except left ventricular mass (LVM) to detect the genetic association with DHF through the effect of left ventricular hypertrophy. PS matched 210 patients with DHF to 210 without. In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype (OR = 1.30, 95% CI = 1.13-1.49, permuted P = 0.003) and the AT1R 1166 CC genotype (OR = 2.61, 95% CI = 1.52-4.45, permuted P < 0.001). Significant gene-gene interaction between the two genes was also detected. However, the ACE gene effect was diminished if LVM was not controlled in the propensity scores. We concluded that genetic variants in the RAS genes may determine individual risk to develop DHF through different pathways. Concomitant presence of ACE DD and AT1R 1166 CC genotypes synergistically increased the predisposition to DHF.

KW - Angiotensin-converting enzyme

KW - Diastolic heart failure

KW - Genetics

KW - Polymorphism

KW - Propensity score

UR - http://www.scopus.com/inward/record.url?scp=67650899268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650899268&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2008.12.033

DO - 10.1016/j.atherosclerosis.2008.12.033

M3 - Article

VL - 205

SP - 497

EP - 502

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

ER -