APOE gene genotype determines influence of smoking on heart disease risk
MedWire News: Individuals who carry the E2 isoform protein allele (ε2) for the apolipoprotein E (APOE) gene have a lower risk for coronary heart disease (CHD) than those who are homozygous for the ε3 allele, while male ε4 carriers have no increased CHD risk, analysis shows.
Specifically, ε2 counteracts CHD risk from smoking in men and women, while ε4 potentiates this risk mainly in women, report Jaana Gustavson (University of Gothenburg, Sweden) and team.
The findings demonstrate how common lifestyle factors can modify the association between genotype and cardiovascular disease risk, they write in the journal Atherosclerosis.
Their analysis comprised 1735 CHD patients and 4654 population controls (3747 men) across two Swedish case-control studies. Each participant completed questionnaires regarding their smoking status (ever [current or former regular] or never) and physical inactivity (amount of time spent mainly sitting).
The researchers also measured the patients' low-density lipoprotein (LDL)-cholesterol levels and identified their APOE genotypes. They evaluated CHD risk using linear regression to examine the effects of APOE polymorphism on LDL-cholesterol levels, and its interaction with smoking, physical inactivity, and overweight (body mass index [BMI] ≥25 kg/m2), respectively.
The findings showed that smoking interacted with APOE on CHD risk. Indeed, ever smokers who carried the ε2 allele were at a 1.45-fold greater risk for CHD than never smokers who carried this allele, those who were homozygous for the ε3 allele had a 2.25-fold greater risk for CHD, and those who carried the ε4 allele a 2.37-fold greater risk for CHD.
Interestingly, the relatively lower smoking-related risk in ε2 participants was seen in men and women. In contrast, there was a more pronounced risk from smoking in female ever smokers carrying the ε4 allele (odds ratio=3.62) but not men, the authors note.
After adjustment for age, gender, study, smoking, and BMI, the odds ratios for physical inactivity were 1.09, 1.34, and 1.79 in ε2, ε3ε3, and ε4 groups, respectively.
Further analysis showed that there was no significant association between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL-cholesterol levels.
Interactions between genotype and cardiovascular disease risk may be of "increasing importance" when assessing risk and advising patients on lifestyle interventions, the authors conclude.
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By Piriya Mahendra