rs776746

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 systematic review examines the role of cytochrome P450 (CYP) gene polymorphisms in the pathogenesis and development of ulcerative colitis. The authors discuss ten critical CYP isoforms (CYP1A1, CYP2D6, CYP2J2, CYP2R1, CYP3A4/3A5/3A7, CYP4F3, CYP24A1, CYP26B1, and CYP27B1) and their genetic variants associated with UC susceptibility and drug metabolism. Notable findings include CYP1A1*2A correlation with UC predisposition, CYP2D6*4 polymorphisms increasing UC risk (OR=1.56), CYP2J2 promoter polymorphism (G-50T) enrichment in UC patients, CYP24A1 variants (rs4809957, rs6068816, rs6091822, rs8124792) showing significant associations in East Asian populations, and CYP27B1 induction in UC lesions.

This pharmacogenetic study examined SNPs in NR1I2, CYP3A4, and CYP3A5 genes in 311 Chinese breast cancer patients undergoing AC (doxorubicin/cyclophosphamide) chemotherapy. The CYP3A5*3 variant rs776746 showed strong association with grade 4 chemotherapy-induced neutropenia in multivariate analysis (OR=2.56, P=0.023), with a 3.14-fold increased risk in A-allele carriers with normal baseline ANC (P=0.004). The study demonstrates gene-environment interaction in chemotherapy toxicity prediction.

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 pharmacogenetic study of 54 Asian nasopharyngeal cancer patients examined how polymorphisms in CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2, and SLCO1B3 affect docetaxel pharmacokinetics and toxicity. Patients homozygous for the variant allele (GG) of SLCO1B3 rs11045585 had significantly higher AUC and lower clearance of docetaxel (P = 0.026 and P = 0.036, respectively). ABCB1 heterozygotes showed the highest decrease in nadir hemoglobin (P = 0.006). The study suggests functional polymorphisms in SLCO1B3 and ABCB1 cooperatively influence docetaxel disposition.

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

A case-control study of 1,090 Caucasian prostate cancer cases examined interactions between genes involved in androgen metabolism/inflammation and benign prostatic hyperplasia (BPH) history on prostate cancer severity. Significant interactions were observed with CYP3A43 P340A (rs680055) and BPH on both Gleason grade (OR=1.82, 95% CI: 1.15–2.87; interaction p=0.026) and tumor stage (OR=3.50, 95% CI: 1.21–10.17; interaction p=0.017), suggesting that androgen metabolism and inflammatory phenotypes act together in determining prostate cancer severity.