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25-10-2011 | Cardiometabolic | Article

Lifestyle factors modify association between APOE gene genotype and CHD


Free abstract

MedWire News: Study findings suggest that smoking and physical inactivity modify the association between apolipoprotein E (APOE) genotype and risk for coronary heart disease (CHD).

The researchers report that the ε2 allele of APOE counteracts the CHD risk associated with smoking and physical inactivity, while the ε4 allele increases this risk.

They say that these findings demonstrate how "common lifestyle factors can modify the association between genotype and cardiovascular disease risk and consequently, that such interactions may be of increasing importance to consider when assessing such risk and advising patients on lifestyle interventions."

Jaana Gustavsson (University of Gothenburg, Sweden) and colleagues combined data from two Swedish case-control studies, including 175 CHD cases and 4654 controls.

All participants completed lifestyle questionnaires containing questions on smoking (ever [current or former regular] or never) and physical inactivity (defined as mainly sitting during leisure time). Individuals were considered overweight if they had a body mass index (BMI) of 25 kg/m2 or more.

The team found that relative to ε3 homozygotes, ε2 carriers had a 37% lower risk for CHD whereas ε4 carriers had no increased risk. This pattern was similar in men and women, and remained significant when adjustments were made for age, gender, study, BMI, smoking, and physical activity.

Compared with those who never smoked, smokers had a 2.14-fold increased risk for CHD. However, this smoking-related risk was lower in ε2 carriers (odds ratio [OR]=1.45) than in ε3 homozygotes (OR=2.25) or ε4 carriers (OR=2.37). Of note, when stratified by gender, the lower risk in ε2 carriers was seen in both men and women whereas a more pronounced risk from smoking was observed in ε4 women (OR=3.62), but not men.

Physical inactivity was associated with a 49% increased risk for CHD. However, this risk differed in the APOE genotype groups, with the risk for CHD only increasing by 9% among physically inactive ε2 carriers, but by 34% and 79% among ε3 homozygotes and ε4 carriers, respectively.

No interaction was seen between overweight and APOE for CHD risk, notes the team.

Writing in the journal Atherosclerosis, the authors say these findings suggest that ε4 carriers may benefit more from physical activity and smoking cessation than people with other APOE genotypes.

"Additional well-designed epidemiological studies of reasonable sample size, as well as future meta-analyses on the emerging cumulated data, will be needed to draw more firm conclusions on these interactions," they conclude.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Nikki Withers