Spring SNPits Summary

The Spring edition of UF Health Personalized Medicine Program's e-newsletter, SNPits is out now. This edition of SNPits summarizes and discusses publications in the American Journal of Health-System Pharmacy, Gastroenterology, and Genetics in Medicine. 

The first publication summary was of a retrospective study that analyzed the pharmacogenetic (PGx) and medication history data from over 20,000 male and female patients of various ethnicities who had been referred to Genelex for pharmacogenetic (PGx) testing. Some patients had genotype information for one CYP gene, while others had genotype information for CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5. The study reports that 93% of the individuals with genotype information for five SNPs were not “normal metabolizers” for at least one CYP isoenzyme, and that older patients were more likely to have potential drug-gene interactions (DGI) or drug-drug-gene interactions (DDGI) as compared to younger patients, likely due to polypharmacy. The authors of the study conclude that the relatively high prevalence of potential and actual DGIs and DDGIs (27.3% of all subjects were found to have at least one physician recommendation to change or consider changing medications due to DGI or DDGI) suggests that PGx testing benefits all patients, and that older patients on multiple drugs are at increased risk for harm. Read the SNPit here. 

The second publication summary was of a study in Dutch patients from 30 hospitals with inflammatory bowel disease (IBD). Thiopurines are standard treatment for IBD and variants in the TPMT gene (TPMT *2, *3A, *3C) are associated with increased hematological adverse reactions (ADRs) such as leukopenia or low platelet counts in patients administered thiopurines. Patients were randomized to receive a standard dose of thiopurines (controls) or TPMT genotype based dosing (intervention). Patients homozygous for the aforementioned TPMT variants received 0-10% of standard dose, and patients heterozygous for those variants received 50% of standard dose. Primary outcomes were the occurrence of a hematological ADR. In a twenty week follow-up the authors found no difference in the proportion of patients with hematological ADRs when comparing between the intervention and control groups (7.4% of the intervention vs 7.9% control; relative risk, 0.93; 95% CI 0.57-1.52). However, when looking exclusively at patients who carried TPMT variants, the proportion of patients that developed ADRs in the intervention was significantly lower (2.6%) as compared to the control group (22.9%) (relative risk, P= 0.11; 95% CI, 0.01-0.85). There was no significant difference in clinical outcome between groups. Read the SNPit here. 

Finally, the third publication summary is of a position statement from the American College of Medical Genetics Board of Directors regarding direct-to-consumer genetic testing, also known as DTC genetic testing. The publication is a revision statement from the ACMG Board of Directors on the use of DTC genetic testing. The revised position statement recognizes the utility of DTC genetic testing, but cautions that several conditions should be met for DTC genetic testing. Read the SNPit here. 

Genotype based dosing guidelines for CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, and TPMT are available at PharmGKB and CPIC.