Allelic polymorphism −491A/T in apo E gene modulates the lipid-lowering response in combined hyperlipidemia treatment

• Published in: European journal of clinical investigation Vol. 32; no. 6; pp. 421 - 428
• Main Authors: García-Otín, A.-L., Civeira, F., Aristegui, R., Díaz, C., Recalde, D., Sol, J. M., Masramon, X., Hernández, G., Pocoví, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2002; Blackwell Publishing Ltd
• Subjects: Adult; Anticholesteremic Agents - therapeutic use; ApoE; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Atorvastatin; bezafibrate; Bezafibrate - therapeutic use; Cholesterol - blood; DNA - analysis; Double-Blind Method; Female; Heptanoic Acids - therapeutic use; Humans; Hyperlipidemia, Familial Combined - drug therapy; Hyperlipidemia, Familial Combined - genetics; Hypolipidemic Agents - therapeutic use; lipid-lowering drugs; Male; Middle Aged; Polymorphism, Genetic; promoter; Promoter Regions, Genetic; Pyrroles - therapeutic use; transcription; Triglycerides - blood
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.2002.00996.x

Background Combined hyperlipidemia (CHL) is one of the dyslipidemias more frequently found in clinical practice, and lipid‐lowering drugs are often necessary in its management. Some genetic loci have been associated with CHL expression, and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms. We have investigated whether common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL. Design One hundred and sixteen subjects participating in the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and common −491A/T and −219T/G polymorphisms in the apo E gene promoter region, Sst I polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations in the LPL gene were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Results Statistical analysis showed the influence of the −491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects carrying the −491T allele showed an increased LDL‐cholesterol‐lowering effect with atorvastatin compared with −491T allele noncarriers (−35% vs. −27%, P = 0·037). Subjects carrying the −491T allele, when on bezafibrate treatment, showed a lower triglyceride reduction compared with −491T allele noncarriers (−23% vs. −39%, P = 0·05). Conclusions In our study, the −491A/T polymorphism in the apo E gene promoter region modulated the lipid‐lowering efficiency of atorvastatin and bezafibrate in CHL patients. Such influence might explain some of the interindividual response variabilities observed for the two drugs, and could help in CHL management.