rs2032583

This PhD thesis comprises multiple studies examining personalized treatment with psychiatric drugs through pharmacogenetics and therapeutic drug monitoring. Two key studies examined: (1) ABCB1 polymorphisms (rs1045642, rs2032582, rs4148739, rs2235040, rs2235015, rs2032583, rs28401781, rs9282564) in relation to antidepressant response in 152 Russian patients with moderate-to-severe depression over 4 weeks, finding rs2235040 and rs4148739 influenced timing of antidepressant response (early vs late). (2) ABCB1 polymorphisms and antipsychotic-induced hyperprolactinemia in Russian schizophrenia patients (N=186), revealing rs2032582 (G2677T) was protective against hyperprolactinemia in the risperidone/paliperidone subgroup. (3) CYP17 polymorphism (rs743572, T34C) and tardive dyskinesia in 146 patients, finding CYP17 CC genotype protective against tardive dyskinesia, though not mediated through DHEA(S) levels.

A candidate gene association study examining ABCB1 (MDR1) gene variants and corticosteroid dependence in 260 pediatric Crohn's disease patients. The rare C allele of rs2032583 conferred protection from corticosteroid dependency (OR=0.56, 95% CI: 0.34-0.95, P=0.029), with the heterozygous TC genotype also protective (OR=0.52, P=0.035). A three-marker haplotype was significantly associated with corticosteroid dependence after multiple comparison correction (P=0.004).

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.

This case-control study of 270 pediatric Crohn's disease cases and 336 controls examined 14 tag-SNPs in the ABCB1/MDR1 gene for associations with disease susceptibility and phenotypes. While SNP rs17327442 showed nominal association with overall CD susceptibility (OR=0.72, P=0.04), this did not withstand multiple testing correction. Two SNPs (rs10248420, rs2032583) were significantly associated with colonic disease location (L2±L4), and five SNPs were nominally associated with noninflammatory disease phenotype. Haplotype analysis revealed specific haplotypes associated with colonic and noninflammatory CD phenotypes.