rs4149056

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.

This study examined genetic and epigenetic markers associated with chemotherapy-induced oral mucositis in 87 pediatric patients with hematological neoplasms, with 81.9% developing mucositis. Global DNA methylation was significantly reduced in children who recovered from mucositis (18% vs 40% in healthy controls, p<0.05), and the DNMT1 rs2228611 SNP showed association with global methylation levels in cancer patients with mucositis history. miR-9-1 and miR-9-3 methylation patterns were associated with tumor status rather than mucositis.

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.

This document is a comprehensive collection of ~1,200 cancer-related research abstracts and summaries published in various journals (2013), covering clinical trials, pharmacogenomic studies, and mutation analyses across multiple cancer types including colorectal, breast, lung, lymphoma, and other malignancies. The collection documents associations between genetic variants (SNPs and somatic mutations), gene expression patterns, and cancer treatment outcomes, including studies on KRAS, EGFR, TP53, BRAF, and pharmacogenomic variants like CYP3A4 and UGT1A1.

This is a comprehensive journal compilation containing multiple oncology and pharmacogenomics studies published in 2013 across various journals. The collection includes 60+ papers covering cancer treatment outcomes, genetic polymorphisms predicting chemotherapy response and survival, pharmacogenetic variants in drug metabolism and DNA repair genes, and prognostic biomarkers in various cancer types including breast, lung, colorectal, hematologic malignancies, and others. Key findings include associations of XRCC1 variants (rs915927, rs76507, rs2854501, rs2854509, rs3213255) with bladder cancer chemotherapy survival, ABCG2 rs2725264 with lung cancer overall survival (HR 3.22), SLCO1B1 rs4149056 with methotrexate pharmacokinetics, MTHFR rs1801131 with acute lymphoblastic leukemia outcome, and ABCC3/GSTM variants with acute myeloid leukemia survival.

GWAS study of 3,294 European ancestry individuals from the eMERGE Network examining serum bilirubin and other liver function tests. Strong association signal at UGT1A1 locus (rs887829, beta=0.15, p=1.30×10^-118) confirmed in both adult and pediatric populations. Additional associations identified in SLCO1B1, SLCO1B3, TDRP, ZMYND8, and ABO locus. Phenome-wide analysis revealed protective effect of TA7 repeat against cerebrovascular disease (OR=0.75, p=0.0008).

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 is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.

This retrospective candidate gene study analyzed 115 Spanish pediatric B-ALL patients treated with high-dose methotrexate (MTX) under the standardized LAL/SHOP protocol. The study examined 10 polymorphisms in 7 genes (MTHFR, TS, SHMT1, RFC1, ABCB1, ABCG2, SLCO1B1) involved in MTX metabolism and their association with MTX toxicity using plasma MTX concentration as an objective marker. The key finding was a statistically significant association between the SLCO1B1 rs11045879 CC genotype and high MTX plasma concentrations (p=0.030 univariate, p=0.008 multivariate), with all patients carrying the CC genotype showing elevated MTX levels. The rs4149081 AA genotype in SLCO1B1 was also associated with high MTX plasma concentrations (p=0.097 univariate, p=0.057 multivariate). No significant associations were found with the other 8 polymorphisms in MTHFR, TS, SHMT1, RFC1, ABCB1, or ABCG2 genes.

This study identified HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) as a major autoantigen in statin-associated immune-mediated necrotizing myopathy (IMNM). Statins up-regulate HMGCR expression in cultured cells, and anti-HMGCR autoantibodies were found in 45 of 750 myopathy patients (6%), with 92% of those age 50+ having prior statin exposure. Notably, the prevalence of the rs4149056 C allele in anti-HMGCR positive patients (0.12) was not increased compared to the general population, indicating this SLCO1B1 SNP is not associated with statin-triggered autoimmune myopathy.

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.