rs2740574

This study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.

A meta-analysis and pooled analysis of case-control studies examining CYP17 (rs743572) and CYP3A4 (rs2740574) polymorphisms in prostate cancer among men of African descent. CYP17 rs743572 showed a 60% increased risk in African-American men (OR 1.6, 95% CI 1.1-2.4) and adjusted OR 3.5 (95% CI 1.2-10.0) in pooled analysis, while CYP3A4 rs2740574 showed no significant association overall or in stratified analyses.

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.

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

A prospective pharmacogenetic study of 69 metastatic breast cancer patients treated with docetaxel plus capecitabine identified CYP1A1 rs1048943 A>G (Ile462Val) as significantly associated with progression-free survival (P=0.0003, HR=0.4 for GA/GG vs AA genotype). While 79 CYP450 SNPs were tested, only this single variant remained significant after Bonferroni correction and multivariate analysis (P=0.004).

Study of 314 German workers (218 bitumen-exposed, 96 non-exposed controls) examining how 18 SNPs in metabolizing enzyme genes modulate urinary PAH metabolites (1-OHP and OHPHE). The CYP1A1 3801T>C CC variant showed 58% higher OHPHE (P=0.051), GSTM1*1 carriers had 11% lower OHPHE (P=0.046), and NAT2*803GG showed 15-16% decrease in OHPHE (P=0.042). No SNPs reached significance for 1-OHP.

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.

Population-based association study of 392 German men examining CYP19A1 and CYP3A4 polymorphisms in relation to benign prostatic hyperplasia (BPH) parameters. rs10046 heterozygotes showed higher PSA levels (2.0 vs 1.7 ng/ml, P=0.012), and CYP3A4 G allele carriers had smaller prostates (27.0 vs 32.1 ml, P=0.02) and lower PSA, though the latter lost significance after multiple testing correction.

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.

A population-based case-control study of 473 African-American men (131 prostate cancer cases, 342 controls) examined SNP associations in six genes involved in androgen and IGF-1 pathways. Significant associations were found between prostate cancer and CYP17 SNPs rs6163, rs6162, and rs743572, with heterozygotes showing decreased risk (P=0.0014, 0.0018, 0.0028). Suggestive evidence for association was found between IGF-1 SNP rs5742657 and prostate cancer (P=0.058 genotype; P=0.02 allelic test). No significant associations were observed for SNPs in CYP3A4, CYP19A1, SRD5A2, or IGFBP-3 genes.