APOE gene polymorphism affects response to lipid-lowering treatment
MedWire News: A polymorphism in the apolipoprotein E (APOE) gene is associated with an attenuated response to lipid-lowering therapy and early referral to lipid clinics, suggests findings of a Portuguese study.
The researchers say that although no differences in lipid profiles were found between carriers of the APOE4 allele and noncarriers at baseline, the former were consistently referred to a lipid clinic at younger ages, and had a significantly smaller reduction in total cholesterol levels after lipid-lowering therapy.
"[Our findings] reinforce the usefulness of APOE genotyping in predicting patients' response to lipid-lowering therapies," explain the authors.
Rui Baptista (Coimbra Hospital Medical School) and colleagues assessed individual APOE genotypes and lipid profiles in 463 dyslipidemic patients admitted to a lipid clinic between 1994 and 2007.
All patients were treated to target lipid levels, as defined by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP)-III guidelines, and followed-up for a median of 3 years.
The frequencies of the ε2, ε3, and ε4 APOE alleles were 7.8%, 78.9%, and 13.3%, respectively.
Patients with one or more copies of the ε4 allele (ε4-carriers) had similar baseline lipid profiles compared with noncarriers. But after the follow-up period, a significantly lower proportion of the ε4-carriers than noncarriers reached the low-density lipoprotein (LDL) targets of less than 130 or 100 mg/dl (3.37 or 2.59 mmol/l, respectively), at 43.2% versus 61.4% and 23.9% versus 34.9%, respectively.
Furthermore, the reduction from baseline in total cholesterol was just 11.8% in the ε4-carriers versus 19.9% in non-carriers.
Similar patterns were also seen for reductions in LDL cholesterol (9.5% vs 17.9%, respectively) and triglycerides (4.6% vs 11.3%), and increases in high-density lipoprotein cholesterol (7.1% vs 11.7%), but these results did not reach statistical significance.
Writing in the journal Lipids in Health and Disease, the researchers note that there was a significant association between presence of the ε4 allele and earlier referral to a lipid clinic; the median age of referral for ε4-carriers was 44.2 years compared with 50.6 years in noncarriers.
The team suggests, therefore, that the combination of a more severe lipid profile at a younger age with a poorer response to an already initiated hypolipidemic treatment strategy may prompt primary care physicians to refer ε4-carriers at an earlier age than noncarriers.
Baptista et al conclude that "intensive therapeutical strategies must be followed to achieve the recommended target goals of lipid levels, particularly in high-risk patients such as ε4 carriers."
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By Nikki Withers