The influence of apolipoprotein B and E gene polymorphisms on the response to simvastatin therapy in patients with hyperlipidemia.
OBJECTIVE
To investigate the effect of apolipoprotein B (apoB) and E (apoE) genetic variations on lipid profile at baseline (before treatment), and also on the subsequent response to simvastatin therapy.


METHODS
Eighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apo B were measured pre-treatment and at the end of the 4th, 8th and 12th post-treatment week. Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism (RFLP).


RESULTS
In all patients, relative frequencies of X- allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of epsilon2 allele was determined as 0.182, epsilon3 as 0.580 and epsilon4 as 0.238. The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment (-23. 9% vs. -13. 6%, P < 0. 05). Compared with patients carrying epsilon3 or epsilon4 allele, those with epsilon2 allele showed a significantly higher percentage in reduction of apoB level after treatment (P < 0.05).


CONCLUSIONS
The relative frequency of apoB X+ allele is high in patients with hyperlipidemia, in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of epsilon2 and epsilon4 are also high in hyperlipidemic patients, and the epsilon2 allele is associated with reduction in apoB level during lipid-relating therapy.
Ye
Ping
P
Department of Geriatric Cardiology, General Hospital of Chinese PLA, Beijing 100853.
Shang
Yanzhong
Y
Ding
Xiaoping
X
D000368:Aged; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin