rs2306283

A meta-analysis of 32 studies (21,692 individuals) examined SNPs associated with statin-induced myopathy (SIM). SLCO1B1 rs4149056 C allele significantly increased SIM risk in heterozygous (OR ~1.58), homozygous (OR ~4.47), dominant (OR ~1.89), and recessive (OR ~4.54) models. SLCO1B1 rs4363657 C allele was protective, and GATM rs9806699 A allele carriers had lower SIM risk with rosuvastatin treatment.

Case-control study of 1,000 Han Chinese individuals (450 epilepsy cases, 550 controls) examining associations between STX1B polymorphisms and epilepsy treatment response. The rs140820592 variant showed significant association with reduced epilepsy risk (OR=0.542, p=0.004) and drug-resistant epilepsy risk (OR=0.260, p=0.004), with eQTL analysis confirming rs140820592 regulates STX1B expression in brain tissues.

A pharmacogenetic study of 143 Brazilian patients with familial hypercholesterolemia receiving atorvastatin examined whether SLCO1B1 haplotypes (rs2306283 and rs4149056) were associated with atorvastatin-induced myalgia. During 12-month follow-up, 14 patients (9.8%) developed myalgia and 16 (11.2%) had creatine kinase elevations >3× normal. No significant associations were found between SLCO1B1 genotypes or haplotypes and either myalgia (OR 2.08 for rs2306283 AG+GG, p=0.24; OR 2.24 for rs4149056 TC+CC, p=0.31) or elevated CK levels, suggesting the pharmacogenetic effect of SLCO1B1 variants is specific to simvastatin rather than atorvastatin.

This study established LightCycler 480-based genotyping methods for two SLCO1B1 polymorphisms (rs2306283 and rs4149056) and determined their frequencies in 366 Tanzanians and 236 Europeans. The rs2306283 (388A>G) polymorphism was much more prevalent in Tanzanians (87% vs 41% in Europeans), while rs4149056 (521T>C) was rare in Tanzanians (6% vs 17% in Europeans). The study found highly significant differences in allelic distribution between the populations (p<0.0001).

This association study investigated polymorphisms in four bilirubin metabolism genes (UGT1A1, HMOX1, BLVRA, SLCO1B1) with serum total bilirubin (TBIL) levels in three Asian populations (502 Kazak, 769 Uyghur, 789 Han). The UGT1A1 (TA)n repeat polymorphism and rs4148323:G>A were strongly associated with TBIL levels across all three populations (P<0.005), with the (TA)7 allele and A allele associated with higher TBIL levels. The (GT)n repeat polymorphism in HMOX1 showed association only in the Uyghur population. The (TA)n repeat and rs4148323 variants together explained 3.9-9.8% of TBIL variation by population.

This study established high-throughput genotyping assays for major SNPs in the SLCO1B1 gene and determined their frequencies in 468 Finnish Caucasian subjects. The c.521T>C SNP (Val174Ala) had an allele frequency of 20.2%, and 26 haplotypes were identified, with the most common haplotype (c.571C) occurring at 35.6% frequency. The functionally significant c.521T>C variant existed in four major haplotypes (*16: 7.9%, *17: 6.9%, *5: 2.7%, *15: 2.4%), which are important for understanding OATP1B1-mediated drug pharmacokinetics and response.