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C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease

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Abstract

Human C-reactive protein (CRP) is a reactant involved in the acute phase response and one of the many molecular factors involved in pathogenesis of coronary artery disease (CAD). CRP gene variants potentially mediate CRP plasma concentrations and the development of CAD. 220 Croatian subjects with angiographically confirmed CAD and 132 control subjects were included in the study. CRP gene polymorphisms 1059G/C and -717G/A were determined by RFLPs, using MaeIII and KspI endonuclease, respectively. Plasma concentrations of CRP and homocysteine were determined by immunoturbidimetry and FPIA, respectively. CRP 1059G/C gene variants were significantly associated with CAD (OR = 0.50; 95% CI = 0.27, 0.94; P = 0.032). Wild GG genotype and rare allele C carrier genotypes were 184 and 22 in CAD(+) group, and 101 and 24 in CAD(−) group, respectively. Multivariate analysis with age, gender, BMI, smoking status, hypertension and diabetes as covariates showed that 1059C carriers had lower CRP concentrations in CAD(−) (P = 0.010) and CAD(+) subjects (P = 0.028). This allele was also significantly associated with lower plasma homocysteine concentrations in both groups (P = 0.018 for CAD(−) and 0.002 for CAD(+). There was no significant difference between CAD(+) and CAD(−) subjects in absolute frequencies for CRP -717A/G gene variant, but multivariate analysis showed that carriers of the rarer G allele had significantly higher CRP plasma concentrations in CAD(−) subjects (P = 0.031) and higher homocysteine concentrations in CAD(+) group (P < 0.001). Atherosclerosis is an inflammatory disease resulting from different genetic and environmental factors. Results presented here support the contribution of CRP genetic variations in the development of CAD.

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Abbreviations

BMI:

Body mass index

CAD:

Coronary artery disease

CRP:

C-reactive protein

ICAM-1:

Intercellular adhesion molecule-1

IL:

Interleukin

HDL-C:

High density lipoprotein cholesterol

LDL-C:

Low density lipoprotein cholesterol

MI:

Myocardial infarction

MCP-1:

Monocyte chemoattractant molecule-1

NF-κB:

Nuclear factor kappaB

TNF-α:

Tumor necrosis factor-α

VCAM-1:

Vascular cell adhesion molecule-1

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Acknowledgments

This investigation was supported by Project Grants No. 108247 and 108-1080316-0298 of the Croatian Ministry of Science, Education and Sport.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Zagreb University School of Medicine, Šalata 3, 10000, Zagreb, Croatia

    Daria Pašalić, Natalija Marinković, Branka Gršković, Goran Ferenčak & Ana Stavljenić-Rukavina

  2. Clinical Institute for Laboratory Diagnosis, Clinical Hospital Center-Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Goran Ferenčak

  3. Department of Cardiology, Magdalena Specialized Hospital for Cardiovascular Surgery and Cardiology, Ljudevita Gaja 2, 49217, Krapinske Toplice, Croatia

    Robert Bernat

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  1. Daria Pašalić
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  2. Natalija Marinković
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  4. Goran Ferenčak
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  5. Robert Bernat
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  6. Ana Stavljenić-Rukavina
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Correspondence to Daria Pašalić.

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Pašalić, D., Marinković, N., Gršković, B. et al. C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease. Mol Biol Rep 36, 775–780 (2009). https://doi.org/10.1007/s11033-008-9244-1

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  • DOI: https://doi.org/10.1007/s11033-008-9244-1

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