Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy

BACKGROUND: The risk of coronary heart disease (CHD) is related to environmental factors and genetic variants. Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol, with some authors suggesting an association between the ε4 allele and CHD. We investigated the relationship between apoE genotype and age at referral to a specialized lipid clinic by the primary care physician and whether the benefits of treatment with statin differed between genotypes. METHODS: We assessed individual apoE genotypes and lipid blood profile in a total of 463 patients followed at a specialized lipid clinic due to dyslipidemia, with a 3-year median follow-up time. The primary care physician at the time of the referral had no access to the apoE genotyping results. Carriers of apoE ε4/ε2 genotype were excluded. RESULTS: The frequencies of ε2, ε3 and ε4 alleles were 7.8, 78.9 and 13.3%, respectively. There were no significant differences between genders. Although with similar lipid profiles and antidyslipidemic drug usage at baseline, ε4-carriers were referred to the clinic at a younger age (44.2 ± 14.7 years) compared with non-ε4 carriers (50.6 ± 13.8 years) (p < 0.001), with a substantially younger age of referral for homozygous E4/4 and for all genotypes with at least one copy of the ε4 allele (p < 0.001 for trend). Although both ε4 and non-ε4 carriers achieved significant reductions in total cholesterol during follow-up (p < 0.001 vs. baseline), the mean relative decrease in total cholesterol levels was higher in non-ε4 carriers (-19.9 ± 2.3%) compared with ε4 carriers (-11.8 ± 2.3%), p = 0.003. CONCLUSION: Our findings support the concept that there is a reduced response to anti-dyslipidemic treatment in ε4 carriers; this can be a contributing factor for the earlier referral of these patients to our specialized lipid clinic and reinforces the usefulness of apoE genotyping in predicting patients response to lipid lowering therapies.