Background-This study evaluates the relationship between cytochrome P450 (CYP) 3A5 genotype and vincristine-induced peripheral neuropathy in children with precursor B cell acute lymphoblastic leukemia (preB ALL). We have shown in vitro that vincristine is metabolized significantly more efficiently by CYP3A5 than by CYP3A4. We also found that vincristine neurotoxicity is less common in African-Americans (70% express CYP3A5) than in Caucasians. We test the hypothesis that CYP3A5 expressers experience less vincristine neuropathy than do CYP3A5 non-expressers.

A genome-wide screen of phosphatases that control mitosis identified CDKN3, which acts through the CDC2 signaling axis.

Objective To determine the impact of maternal and fetal single nucleotide polymorphisms (SNPs) in key betamethasone (BMZ) pathways on neonatal outcomes. Study design DNA was obtained from women given BMZ and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome (RDS) was performed. Results 109 women delivering 117 babies were analyzed. Sixty-four babies (49%) developed RDS. Multivariable analysis revealed that RDS was associated with maternal SNPs in CYP3A5 (OR 1.63, 95%CI 1.16–2.30) and the glucocorticoid receptor (OR 0.28, 95%CI0.08–0.95) and fetal SNPs in ADCY9 (OR 0.17, 95%CI 0.03–0.80) and CYP3A7*1E (rs28451617, OR 23.68, 95%CI 1.33–420.6). Conclusion Maternal and fetal genotypes are independently associated with neonatal RDS after treatment with BMZ for preterm labor.

OBJECTIVE We previously demonstrated that maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome (RDS). The objective of the current study is to determine the impact of maternal and fetal single nucleotide polymorphisms (SNPs) in key betamethasone (BMZ) pathways on respiratory outcomes that serve as markers for severity of disease. STUDY DESIGN DNA was obtained from women given BMZ and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis controlling for relevant clinical variables to determine SNP impact on bronchopulmonary dysplasia (BPD), need for respiratory support, and surfactant therapy use was performed. RESULTS 109 women delivering 117 infants were analyzed. 14.5% of the infants developed BPD, 70.8% needed some respiratory support after birth, and 27.5% needed surfactant. In a multivariable regression analysis, gestational age at delivery was associated with most neonatal respiratory outcomes (p≤0.01) and chorioamnionitis was associated with BPD (p<0.03). Genotypes associated with respiratory severity outcomes were as follows: BPD- Fetal IPO13 (rs4448553; OR 0.01, 95% CI 0.00–0.92); Surfactant use- Maternal IPO13 (rs2428953 and 2486014; OR 13.8, 95%CI 1.80–105.5 and OR 35.5, 95% CI 1.71–736.6, respectively). CONCLUSIONS Several discrete maternal and fetal SNPs in the Importin 13 gene (IPO13) may be associated with neonatal respiratory outcomes after maternal antenatal corticosteroid treatment for anticipated preterm birth.