rs2231142

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.

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

This pilot study investigated associations between genetic polymorphisms in transporter genes (SLC19A1, ABCC2, ABCB1, ABCC1, ABCC3, ABCG2) and clinical response to methotrexate (MTX) in 100 Chinese rheumatoid arthritis (RA) patients. Multiple SNPs showed significant associations with MTX response: SLC19A1 rs12659 and rs3788200 major alleles were associated with EULAR good/moderate response (RR=1.42-1.45, p=0.03-0.04); ABCC2 rs3740066 major allele was associated with DAS28-ESR low disease activity (RR=0.67, p=0.02). Haplotype analysis identified significant associations of SLC19A1 and ABCC2 haplotypes with clinical response outcomes.

This genome-wide association study of 4,446 allopurinol-treated subjects identified BCRP Q141K (rs2231142) as a significant determinant of poor allopurinol response (P = 8.06 × 10⁻¹¹), with a novel suggestive association in GREM2 (rs1934341, P = 3.22 × 10⁻⁶) for better response. In vitro studies demonstrated that oxypurinol inhibits GLUT9-mediated uric acid uptake (IC₅₀ = 108 µM), suggesting a secondary mechanism of allopurinol action beyond xanthine oxidase inhibition.

This replication study analyzed 2255 variants in LD with GWAS-identified gout/serum urate susceptibility loci in 1255 Han Chinese gout patients and 1848 controls. Twenty-three variants (41%) showed nominal association (p<0.05), with the strongest signal at ABCG2 rs1481012 (p=8.96×10⁻¹¹, OR=1.890). Previous gout-associated loci including ABCG2, SLC2A9, GCKR, ALDH2, and CNIH2 were replicated, while cumulative genetic risk scores showed that individuals with ≥8 risk alleles had significantly increased gout risk (OR=16.361 for ≥12 alleles).

A genome-wide association study of 2,027 subjects from the Kaiser Permanente GERA cohort identified ABCG2 as a key determinant of allopurinol response for treating hyperuricemia/gout. The missense variant rs2231142 (Q141K) was significantly associated with reduced serum uric acid reduction (P = 3 × 10^-7 in meta-analysis, accounting for 1.1% of variance). Functional studies confirmed that BCRP (encoded by ABCG2) transports allopurinol and oxypurinol, and the Q141K variant reduces this transport.

This dissertation examined pharmacogenetic associations with clozapine adverse effects in 237 Finnish schizophrenia patients. ADRA2A rs1800544 was associated with clozapine-induced sialorrhea (OR 2.13, 95% CI: 1.17-3.88, p=0.013). Eight HNMT SNPs in complete linkage disequilibrium (r²=1) were associated with sedation. CHRM3 rs685548 and weighted genetic risk scores from HTR4, HTR7, TPH1, CHRM2, ABCB1, and OPRM1 were associated with anticholinergic symptoms.

A two-part genetic association study in Korean populations examining SNP associations with serum uric acid (SUA) concentration. Study 1 compared minor allele frequencies of 40 SNPs associated with SUA across Korean, Japanese, and European descent populations in 1,957 subjects. Study 2 analyzed associations in 402 RA patients, finding rs12734001 (PPP1R12B) most significantly associated with SUA levels (P_trend = 2.29 × 10^-9) and rs3741414 (INHBC) with P_trend = 0.01. Results showed Korean SNP frequencies were more similar to Japanese than European populations.

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 study analyzed 9 uric acid-regulating SNPs and 5 progranulin-regulating SNPs in 1,061 Parkinson's disease patients and 754 controls. A cumulative genetic risk score from 8 SNPs (SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A/SCGN rs742132, SLC16A9 rs12356193) was significantly associated with increased PD risk (OR=1.55, p=0.012). The TMEM106b rs1020004 variant showed association with PD risk (p=0.003), and SORT1 rs646776 was associated with serum progranulin levels and PD-dementia risk.

This replication study examined 2,255 variants in linkage disequilibrium with GWAS-identified gout/urate susceptibility loci in 1,255 Han Chinese gout patients and 1,848 controls. Twenty-three variants (41% of 56 LD-pruned variants) showed nominal association with gout (p < 0.05), with the strongest signals at ABCG2 (rs1481012, OR=1.890, p=8.96×10⁻¹¹) and SLC2A9 (rs11722228, OR=1.619, p=2.40×10⁻⁶). Cumulative genetic risk score analysis demonstrated increasing gout risk with growing numbers of risk alleles (OR=16.361 for ≥12 alleles vs ≤5 reference).

This study of 102 Mexican breast cancer patients undergoing FAC neoadjuvant chemotherapy found that ABCB1 rs1045642 (C3435T) polymorphism was significantly associated with chemotherapy response. Patients with C/C or C/T genotypes were more likely to be chemosensitive than T/T carriers (OR=4.055, p=0.0064). The C/C+C/T genotype was protective against chemoresistance in pathological response (OR=3.714, p=0.0104). ABCG2 rs2231142 (G421T) showed no significant association with chemotherapy response.

This comprehensive study genotyped 53 polymorphisms in three ABC transporter genes (ABCB1, ABCC2, and ABCG2) in 377 lung cancer patients (206 NSCLC and 171 SCLC) to assess their impact on chemotherapy response and survival. SNP rs717620 in ABCC2 was strongly associated with shorter progression-free survival and overall survival in SCLC patients but not NSCLC, indicating ABCC2 genetic variation is an important factor in SCLC survival following chemotherapy.

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 case-control and family-based study evaluated 64 SNPs in 34 genes for associations with spina bifida in 558 Irish case-families and 994 controls. Spina bifida was significantly associated with LEPR rs1805134 (GRR: 1.5, P = 0.0264) and COMT rs737865 (GRR: 1.4, P = 0.0206), with additional confirmations of previous findings in MTHFR 677C>T and other genes, suggesting roles for leptin signaling and methylation pathways in neural tube defect pathogenesis.