Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Abstract

AimsThe relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated.Material and MethodsOne-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR.ResultsSubjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05).ConclusionSLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

Association between <i>SLCO1B1 521 T</i>＞<i>C</i> and <i>388 A</i>＞<i>G </i>Polymorphisms and Statins Effectiveness: A Meta-Analysis

“…Thus, well-designed original studies involving more ethnicities and larger sample sizes are needed to confirm our findings. [30] short-term [25] [30] short-term [20,21,25,28] [30] short-term [25] [30] short-term [24,25] [30] short-term [24,31] [30] short-term [24,31] [30] short-term [24,31] [30] short-term [24,31] [30] short-term [22,24,31] [30] short-term [22,24,31] [30] short-term [22,24,29,31] [30] short-term [22,24,31] [30] short-term [24,31] 1 2 2.43 [ 16.59, 11.73] 3.00 [ 14.26, 8.26] 0.74 0.60 AG: AA long-term [30] short-term [24,31] …”

“…To explore the effect of ethnicity on the effectiveness of statins with different genotypes, we excluded the studies involving Asian populations and a statistically significant association between the 521 T C polymorphism and statin effectiveness of lowering LDL-C was found in the dominant model, the recessive model and the homozygote comparison. Thus, [19,22,24,26,27,30,31] AG: AA [19,22,24,26,27,30,31] GG: AA AG [19,22,24,26,27,[29][30][31] GG AG: AA [19,22,24,26,27,30,31] [22,24,30,31] AG: AA [22,24,30,31] GG: AA AG [22,24,[29][30][31] GG AG: AA [22,24,30,31] 2.84 ( 6.37, 0.68) [24,30,…”

“…Two studies 25,29) calculated the percentage change with p ((baseline after treatment)/ baseline) 100%, so we adjusted their minus signs. In addition, the mean SD for all of the results were obtained.…”

“…To reduce the cardiovascular risk, various regimens of adjusted lifestyle have been recommended (such as smoking cessation, limiting alcohol and dietary Rong Dai and Jing Feng contributed equally to this work. ing therapy 29,30) . Specially, Shabana et al maintained that the polymorphism showed gender-related effects on TG change following the atorvastatin treatment 31) .…”

Aspects of Lipid-Lowering Therapy With Atorvastatin in Patients With Myocardial Infarction From the Perspective of Personalized Medicine

“…также приводят сведения о не-значительной вариабельности липидспижающего от-вета на терапию правастатином [10]. Различий между генотипами на фоне лечения аторвастатином не обна-ружили и бразильские ученые [11]. В крупном иссле-довании SEARCH, охватывающем более 16000 рес-пондентов, оценивалось влияние симвастатина на по-казатели липидного спектра крови в зависимости от по-лиморфного маркера SLCO1B1.…”