Intronic variants in SLCO1B1 related to statin-induced myopathy are associated with the low-density lipoprotein cholesterol response to statins in Chinese patients with hyperlipidaemia.
Whole-genome studies have identified several intronic single nucleotide polymorphisms (SNPs) in SLCO1B1 associated with simvastatin-induced myopathy. The present study determined the effect of an intronic SNP rs4149081 in SLCO1B1 on the lipid-lowering effects of simvastatin and rosuvastatin in Chinese patients with hypercholesterolaemia. Lipid profiles were determined off treatment and after at least 4 weeks of treatment with each of the statins at daily doses of rosuvastatin 10 mg and simvastatin 40 mg. In 247 patients with good adherence, the rs4149081 G>A polymorphism was significantly associated with a 4.6 and 4.0% greater low-density lipoprotein cholesterol (LDL-C) reduction compared with those with wild-type alleles in response to rosuvastatin and simvastatin, respectively (P<0.05 for both). The 388A>G and 521T>C polymorphisms were not associated with the LDL-C response to either statin. The intronic SNP rs4149081 in SLCO1B1 was associated with the LDL-C response to statins in Chinese patients and this association was independent of the 521T>C polymorphism.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR.
Miao
M
Hu
Valiant W L
VW
Mak
Brian
B
Tomlinson
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People; D008078:Cholesterol, LDL / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D014644:Genetic Variation; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics; D007438:Introns; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced* / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011743:Pyrimidines; C503999:SLCO1B1 protein, human; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D019821:Simvastatin