Pasanen Marja K, Miettinen Tatu A, Gylling Helena, Neuvonen Pertti J, Niemi Mikko
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Pharmacogenet Genomics. 2008 Oct;18(10):921-6. doi: 10.1097/FPC.0b013e32830c1b5f.
We investigated the influence of SLCO1B1 polymorphism on cholesterol synthesis and absorption during baseline, and as affected by statins. In a crossover study, 32 healthy volunteers with different SLCO1B1 genotypes ingested a single dose of fluvastatin, pravastatin, simvastatin, rosuvastatin, and atorvastatin. Plasma total cholesterol, and cholesterol synthesis and absorption markers were measured before statin administration and up to 12 h thereafter. The mean fasting baseline plasma desmosterol to cholesterol ratio was 40% higher in participants with the SLCO1B1 c.521CC variant genotype than in those with the c.521TT genotype (P=0.043). The genotype had no significant effect on cholesterol absorption markers. All statins decreased lathosterol and avenasterol to cholesterol ratios, but no significant differences in the response existed between SLCO1B1 genotypes. In conclusion, the low activity SLCO1B1 c.521CC genotype is associated with an increased cholesterol synthesis rate. The short-term effects of statins on cholesterol homeostasis were not associated with the SLCO1B1 polymorphism.
我们研究了SLCO1B1基因多态性在基线期以及受他汀类药物影响时对胆固醇合成和吸收的作用。在一项交叉研究中，32名具有不同SLCO1B1基因型的健康志愿者分别单次服用氟伐他汀、普伐他汀、辛伐他汀、瑞舒伐他汀和阿托伐他汀。在服用他汀类药物前及之后长达12小时内测量血浆总胆固醇以及胆固醇合成和吸收标志物。与携带c.521TT基因型的参与者相比，携带SLCO1B1 c.521CC变异基因型的参与者空腹基线期血浆去氢胆固醇与胆固醇的平均比值高40%（P=0.043）。该基因型对胆固醇吸收标志物无显著影响。所有他汀类药物均降低了羊毛甾醇和燕麦甾醇与胆固醇的比值，但SLCO1B1各基因型之间的反应无显著差异。总之，低活性的SLCO1B1 c.521CC基因型与胆固醇合成速率增加有关。他汀类药物对胆固醇稳态的短期影响与SLCO1B1基因多态性无关。
