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Published on: February 25, 2016
Smoking-dependent association between paraoxonase 1 M/L55 genotype and coronary atherosclerosis in males: an autopsy
Riikka Rontu1, Pekka J Karhunen, Erkki Ilveskoski
1Laboratory of Atherosclerosis Genetics, Tampere University Hospital, FinnMedi 2, PO Box 2000, FIN-33521, Tampere, Finland. riikka.malin@csc.fi
Abstract:
High-density lipoprotein-associated paraoxonase 1 (PON1) enzyme can retard the oxidation of lipids. The methionine for leucine substitution at position 55 (M/L55) of the PON1 protein is associated with lower (MM genotype) or higher (ML or LL genotype) expression of the gene affecting serum level of PON1. We studied the association of the PON1 M/L55 genotype with the extent of atherosclerosis in an autopsy series of Finnish males. Areas of the coronary arteries and the aorta covered with fatty streaks and fibrotic and complicated lesions were measured from a total of 700 cases. Carriers of the MM genotype (14.4% of subjects) had larger percentual areas of fatty streaks in their left anterior descending coronary artery (P=0.014) and right coronary artery (P=0.004), as well as in thoracic (P<0.001) and abdominal aorta (P=0.010) compared to carriers of the LL or ML genotype. A PON1 genotype-by-smoking interaction was observed on the area of fatty streaks in left anterior descending coronary artery (P=0.011) and right coronary artery (P=0.005); the association between fatty streaks and MM genotype was evident only among non-smokers, whereas in smokers this association was abolished. The areas of more advanced atherosclerotic lesions did not vary significantly between the genotype groups. These data suggest that the genetic variation of PON1 affects the formation of early atherosclerotic lesions and that the effect is modified by smoking.
Insights
The paraoxonase 1 (PON1) MM genotype is linked to more early atherosclerosis in Finnish men. Smoking negates this genetic effect on fatty streaks in coronary arteries and aorta.
Area of Science:
- Cardiovascular Genetics
- Atherosclerosis Research
- Biomarker Discovery
Background:
- Paraoxonase 1 (PON1) is an enzyme associated with high-density lipoprotein that inhibits lipid oxidation.
- The PON1 M/L55 polymorphism influences PON1 gene expression and serum PON1 levels.
- Genetic variations in PON1 may impact the development of atherosclerosis.
Purpose of the Study:
- To investigate the association between the PON1 M/L55 genotype and the extent of atherosclerosis.
- To examine the interaction between PON1 genotype and smoking on atherosclerotic lesion development.
Main Methods:
- Autopsy series of 700 Finnish males.
- Quantification of fatty streaks and advanced lesions in coronary arteries and aorta.
- Genotyping for the PON1 M/L55 polymorphism.
Main Results:
- Carriers of the MM genotype exhibited significantly larger areas of fatty streaks in coronary arteries and aorta compared to LL or ML genotypes.
- A significant interaction between PON1 genotype and smoking was observed; the MM genotype's association with fatty streaks was only apparent in non-smokers.
- No significant differences in advanced atherosclerotic lesions were found between genotype groups.
Conclusions:
- Genetic variation in PON1, specifically the M/L55 polymorphism, influences the formation of early atherosclerotic lesions (fatty streaks).
- Smoking modifies the effect of the PON1 genotype on early lesion development, abolishing the association in smokers.
- PON1 genotype may serve as a risk factor for early atherosclerosis, with its impact modulated by smoking status.
