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The M235T polymorphism of the AGT gene modifies the risk of coronary artery disease associated with the presence of hypercholesterolemia

  • Cardiovascular Disease
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Abstract

Objective Atherosclerosis is an inflammatory disease resulting from interactions between various genetic and non-genetic factors. Angiotensinogen gene (AGT) belongs to polymorphic candidate genes. Recent evidence show that many traditional risk factors of coronary artery disease (CAD) influence synthesis of AGT. This report focuses on the interactions between M235T polymorphism of AGT gene and traditional risk factors of CAD. Material and Methods 255 subjects, including 158 patients with angiographically confirmed CAD and 97 blood donors without history of cardiovascular diseases were studied. M235T polymorphism of the AGT gene was genotyped using PCR-RFLP method. To determine the possible interactions of AGT genotypes and traditional risk factors of CAD the attributable proportion due to interaction (AP) and synergy models were used. Results The frequency of 235T allele carriers was significantly higher in patients than in controls (77.8 vs. 62.9, OR = 2.20, 95%CI; 1.10–4.40, P = 0.026, in multivariate logistic regression model). We found the existence of interaction between the 235T allele carrier-state and hypercholesterolemia (total cholesterol ≥5 mmol/l) increasing the risk of CAD (SI = 3.39, 95%CI; 1.33–8.66, AP = 0.65, 95%CI; 0.39–0.91). The 235T allele also interacted with elevated LDL cholesterol levels (≥3 mmol/l) (AP = 0.49, 95%CI; 0.20–0.96), but not with the hypertension, overweight/obesity and cigarette smoking. Conclusion The 235T allele increases the risk of CAD associated with the presence of hypercholesterolemia.

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Abbreviations

AGT:

Angiotensinogen

AP:

Attributable proportion due to interaction

CAD:

Coronary artery disease

LDL:

Low density cholesterol lipoprotein

Ox-LDL:

Oxidized low density cholesterol lipoprotein

RAS:

Renin angiotensin system

SI:

Synergy index

TC:

Total cholesterol

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Acknowledgement

Supported by the Medical University of Silesia within the projects: NN-2-102/05 and NN-2-016/06.

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Authors and Affiliations

  1. Department of Biochemistry and Medical Genetics, Medical University of Silesia, Medykow Str 18, 40-752, Katowice, Poland

    Pawel Niemiec & Iwona Zak

  2. The First Department and Clinic of Cardiology in Upper Silesian Center of Cardiology in Katowice, Medical University of Silesia, Ziolowa Str 45/47, 40-635, Katowice, Poland

    Krystian Wita

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  1. Pawel Niemiec
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Correspondence to Pawel Niemiec.

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Niemiec, P., Zak, I. & Wita, K. The M235T polymorphism of the AGT gene modifies the risk of coronary artery disease associated with the presence of hypercholesterolemia. Eur J Epidemiol 23, 349–354 (2008). https://doi.org/10.1007/s10654-008-9241-7

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  • DOI: https://doi.org/10.1007/s10654-008-9241-7

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