Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction

Sungha Park, Jong Chan Youn, Dong Jik Shin, Chan Mi Park, Jung Sun Kim, Young Guk Ko, Donghoon Choi, Jong Won Ha, Yangsoo Jang, Namsik Chung

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight, zinc-binding matrix metalloproteinase that is known to be abundantly expressed in ruptured plaques. Previous studies have shown PAPP-A to be a significant marker of plaque instability and cardiovascular events in patients with acute coronary syndromes. Because the activity of PAPP-A may be modulated by genetic variants in the PAPP-A genes, we tried to determine the association of PAPP-A gene with acute myocardial infarction (AMI). METHODS: We analyzed four single nucleotide polymorphisms (SNPs) of PAPP-A gene variants and seven other polymorphisms of cytokine genes that have been reported to have functional significance (RANTES G-403A, MCP1 G-2518A, CRP A2147G, CRP G-717A, AGER G557A, LTA T26A, IL-6 G-572C) for possible association with AMI in 170 unrelated AMI patients and unrelated age-matched controls, respectively. RESULTS: The average age of the study population was 62.2±11.4 years in AMI patients and 62.6±10.4 years in healthy controls. Multiple logistic regression analysis with risk factors such as age, male sex, smoking, hypertension, diabetes mellitus, and dyslipidemia revealed the PAPP-A IVS6+95 C allele to be associated with an increased risk of AMI (dominancy: odds ratio, 2.13; 95% confidence interval, 1.12-4.07; P=0.022; codominancy: odds ratio, 1.89; 95% confidence interval, 1.14-3.16; P=0.015). CONCLUSIONS: We found, for the first time, that PAPP-A IVS6+95 C allele is an independent risk factor for AMI even after adjustment for traditional risk factors. The determination of such genotype contributing to AMI could provide a new tool for identifying high-risk individuals.

Original languageEnglish
Pages (from-to)417-422
Number of pages6
JournalCoronary artery disease
Volume18
Issue number6
DOIs
Publication statusPublished - 2007 Sep 1

Fingerprint

Pregnancy-Associated Plasma Protein-A
Genetic Polymorphisms
Myocardial Infarction
Alleles
Odds Ratio
vif Genes
Confidence Intervals
Genes
Chemokine CCL5
Acute Coronary Syndrome
Dyslipidemias
Matrix Metalloproteinases
Single Nucleotide Polymorphism
Zinc
Blood Proteins
Interleukin-6
Diabetes Mellitus
Molecular Weight
Logistic Models
Smoking

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Park, Sungha ; Youn, Jong Chan ; Shin, Dong Jik ; Park, Chan Mi ; Kim, Jung Sun ; Ko, Young Guk ; Choi, Donghoon ; Ha, Jong Won ; Jang, Yangsoo ; Chung, Namsik. / Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction. In: Coronary artery disease. 2007 ; Vol. 18, No. 6. pp. 417-422.
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title = "Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction",
abstract = "BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight, zinc-binding matrix metalloproteinase that is known to be abundantly expressed in ruptured plaques. Previous studies have shown PAPP-A to be a significant marker of plaque instability and cardiovascular events in patients with acute coronary syndromes. Because the activity of PAPP-A may be modulated by genetic variants in the PAPP-A genes, we tried to determine the association of PAPP-A gene with acute myocardial infarction (AMI). METHODS: We analyzed four single nucleotide polymorphisms (SNPs) of PAPP-A gene variants and seven other polymorphisms of cytokine genes that have been reported to have functional significance (RANTES G-403A, MCP1 G-2518A, CRP A2147G, CRP G-717A, AGER G557A, LTA T26A, IL-6 G-572C) for possible association with AMI in 170 unrelated AMI patients and unrelated age-matched controls, respectively. RESULTS: The average age of the study population was 62.2±11.4 years in AMI patients and 62.6±10.4 years in healthy controls. Multiple logistic regression analysis with risk factors such as age, male sex, smoking, hypertension, diabetes mellitus, and dyslipidemia revealed the PAPP-A IVS6+95 C allele to be associated with an increased risk of AMI (dominancy: odds ratio, 2.13; 95{\%} confidence interval, 1.12-4.07; P=0.022; codominancy: odds ratio, 1.89; 95{\%} confidence interval, 1.14-3.16; P=0.015). CONCLUSIONS: We found, for the first time, that PAPP-A IVS6+95 C allele is an independent risk factor for AMI even after adjustment for traditional risk factors. The determination of such genotype contributing to AMI could provide a new tool for identifying high-risk individuals.",
author = "Sungha Park and Youn, {Jong Chan} and Shin, {Dong Jik} and Park, {Chan Mi} and Kim, {Jung Sun} and Ko, {Young Guk} and Donghoon Choi and Ha, {Jong Won} and Yangsoo Jang and Namsik Chung",
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Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction. / Park, Sungha; Youn, Jong Chan; Shin, Dong Jik; Park, Chan Mi; Kim, Jung Sun; Ko, Young Guk; Choi, Donghoon; Ha, Jong Won; Jang, Yangsoo; Chung, Namsik.

In: Coronary artery disease, Vol. 18, No. 6, 01.09.2007, p. 417-422.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction

AU - Park, Sungha

AU - Youn, Jong Chan

AU - Shin, Dong Jik

AU - Park, Chan Mi

AU - Kim, Jung Sun

AU - Ko, Young Guk

AU - Choi, Donghoon

AU - Ha, Jong Won

AU - Jang, Yangsoo

AU - Chung, Namsik

PY - 2007/9/1

Y1 - 2007/9/1

N2 - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight, zinc-binding matrix metalloproteinase that is known to be abundantly expressed in ruptured plaques. Previous studies have shown PAPP-A to be a significant marker of plaque instability and cardiovascular events in patients with acute coronary syndromes. Because the activity of PAPP-A may be modulated by genetic variants in the PAPP-A genes, we tried to determine the association of PAPP-A gene with acute myocardial infarction (AMI). METHODS: We analyzed four single nucleotide polymorphisms (SNPs) of PAPP-A gene variants and seven other polymorphisms of cytokine genes that have been reported to have functional significance (RANTES G-403A, MCP1 G-2518A, CRP A2147G, CRP G-717A, AGER G557A, LTA T26A, IL-6 G-572C) for possible association with AMI in 170 unrelated AMI patients and unrelated age-matched controls, respectively. RESULTS: The average age of the study population was 62.2±11.4 years in AMI patients and 62.6±10.4 years in healthy controls. Multiple logistic regression analysis with risk factors such as age, male sex, smoking, hypertension, diabetes mellitus, and dyslipidemia revealed the PAPP-A IVS6+95 C allele to be associated with an increased risk of AMI (dominancy: odds ratio, 2.13; 95% confidence interval, 1.12-4.07; P=0.022; codominancy: odds ratio, 1.89; 95% confidence interval, 1.14-3.16; P=0.015). CONCLUSIONS: We found, for the first time, that PAPP-A IVS6+95 C allele is an independent risk factor for AMI even after adjustment for traditional risk factors. The determination of such genotype contributing to AMI could provide a new tool for identifying high-risk individuals.

AB - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight, zinc-binding matrix metalloproteinase that is known to be abundantly expressed in ruptured plaques. Previous studies have shown PAPP-A to be a significant marker of plaque instability and cardiovascular events in patients with acute coronary syndromes. Because the activity of PAPP-A may be modulated by genetic variants in the PAPP-A genes, we tried to determine the association of PAPP-A gene with acute myocardial infarction (AMI). METHODS: We analyzed four single nucleotide polymorphisms (SNPs) of PAPP-A gene variants and seven other polymorphisms of cytokine genes that have been reported to have functional significance (RANTES G-403A, MCP1 G-2518A, CRP A2147G, CRP G-717A, AGER G557A, LTA T26A, IL-6 G-572C) for possible association with AMI in 170 unrelated AMI patients and unrelated age-matched controls, respectively. RESULTS: The average age of the study population was 62.2±11.4 years in AMI patients and 62.6±10.4 years in healthy controls. Multiple logistic regression analysis with risk factors such as age, male sex, smoking, hypertension, diabetes mellitus, and dyslipidemia revealed the PAPP-A IVS6+95 C allele to be associated with an increased risk of AMI (dominancy: odds ratio, 2.13; 95% confidence interval, 1.12-4.07; P=0.022; codominancy: odds ratio, 1.89; 95% confidence interval, 1.14-3.16; P=0.015). CONCLUSIONS: We found, for the first time, that PAPP-A IVS6+95 C allele is an independent risk factor for AMI even after adjustment for traditional risk factors. The determination of such genotype contributing to AMI could provide a new tool for identifying high-risk individuals.

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