rs12248560

This paper presents the development and validation of a Tetra-primer ARMS-PCR (T-ARMS-PCR) method to detect the CYP2C19*17 polymorphism (rs12248560, -806C>T), which confers ultrarapid metabolization of drugs like clopidogrel and omeprazole. In 93 samples, T-ARMS-PCR detected 91 CC genotypes (97.8%) and 2 CT genotypes (2.2%), with C and T allele frequencies of 98.9% and 1.1% respectively. All T-ARMS-PCR results were concordant with DNA sequencing validation.

Study of 25 multiple myeloma patients examined CYP2C19 genotype-phenotype discordance using three common variants (rs4244285, rs49486893, rs12248560). Despite no homozygous null genotypes, 28% of patients showed poor metabolizer phenotype measured by proguanil metabolic ratio, indicating acquired loss of CYP2C19 activity independent of genetic variation (p < 0.0001). Discordance did not correlate with inflammatory markers CRP or IL-6.

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.

A candidate gene study of 34 patients with neuropathic pain found significant association between the serotonin receptor 2C gene (HTR2C rs6318 C allele) and pain relief during escitalopram treatment, with an odds ratio of 15.5 (p=0.014) in men and 10.6 (p=0.010) in combined analysis. Additional genes in the serotonergic pathway including HTR2A, SLC6A4 (5-HTTLPR), CYP2C19, and ABCB1 were also analyzed, with 5-HTTLPR showing a borderline association.

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.

This genome-wide association study identified the CYP2C19*2 loss-of-function variant (rs4244285) as a major determinant of clopidogrel response in 429 Amish individuals. The variant was associated with diminished platelet aggregation response to ADP stimulation (P=4.3×10⁻¹¹) and accounted for 12% of variation in clopidogrel response. In an independent cohort of 227 patients undergoing percutaneous coronary intervention, carriers of CYP2C19*2 had higher cardiovascular event rates (20.9% vs 10.0%, HR=2.42, P=.02).

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.

An association study of 201 warfarin-treated patients found that polymorphisms in VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, and APOE were significantly associated with warfarin dose requirement (P < 0.000175 for VKORC1 and CYP2C9). A multiple regression model incorporating VKORC1, CYP2C9, PROC, and non-genetic factors (age, bodyweight, drug interactions, treatment indication) accounted for 62% of the variance in warfarin dose.