Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population: The hisayama study

Hideki Kondo, Toshiharu Ninomiya, Jun Hata, Yoichiro Hirakawa, Koji Yonemoto, Hisatomi Arima, Masaharu Nagata, Kazuhiko Tsuruya, Takanari Kitazono, Yutaka Kiyohara

Research output: Contribution to journalArticle

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Abstract

Aim: The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. Methods: The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. Results: A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000 person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval =2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID+II genotype; P for interaction = 0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. Conclusions: The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

Original languageEnglish
Pages (from-to)390-403
Number of pages14
JournalJournal of atherosclerosis and thrombosis
Volume22
Issue number4
DOIs
Publication statusPublished - Jan 1 2014

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Peptidyl-Dipeptidase A
Hypercholesterolemia
Polymorphism
Coronary Disease
Genes
Genotype
Population
Medical problems
Smoking
Hazards
Hypertension
Independent Living
Incidence
Cardiovascular Diseases
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population : The hisayama study. / Kondo, Hideki; Ninomiya, Toshiharu; Hata, Jun; Hirakawa, Yoichiro; Yonemoto, Koji; Arima, Hisatomi; Nagata, Masaharu; Tsuruya, Kazuhiko; Kitazono, Takanari; Kiyohara, Yutaka.

In: Journal of atherosclerosis and thrombosis, Vol. 22, No. 4, 01.01.2014, p. 390-403.

Research output: Contribution to journalArticle

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abstract = "Aim: The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. Methods: The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. Results: A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000 person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95{\%} confidence interval =2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95{\%} CI=1.04-2.12 for hypercholesterolemia with the ID+II genotype; P for interaction = 0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. Conclusions: The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.",
author = "Hideki Kondo and Toshiharu Ninomiya and Jun Hata and Yoichiro Hirakawa and Koji Yonemoto and Hisatomi Arima and Masaharu Nagata and Kazuhiko Tsuruya and Takanari Kitazono and Yutaka Kiyohara",
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T1 - Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population

T2 - The hisayama study

AU - Kondo, Hideki

AU - Ninomiya, Toshiharu

AU - Hata, Jun

AU - Hirakawa, Yoichiro

AU - Yonemoto, Koji

AU - Arima, Hisatomi

AU - Nagata, Masaharu

AU - Tsuruya, Kazuhiko

AU - Kitazono, Takanari

AU - Kiyohara, Yutaka

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Aim: The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. Methods: The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. Results: A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000 person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval =2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID+II genotype; P for interaction = 0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. Conclusions: The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

AB - Aim: The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. Methods: The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. Results: A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000 person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval =2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID+II genotype; P for interaction = 0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. Conclusions: The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

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