Influence of Leukotriene Pathway Polymorphisms on Response to Montelukast in Asthma

• DOI: 10.1164/rccm.200509-1412oc
• Publication Date: 2005-11-18T01:44:49Z
• Authors: John J. Lima; Shu Zhang; Audrey Grant; Lianhe Shao; Kelan G. Tantisira; Hooman Allayee; Jianwei Wang; James Sylvester; Janet Holbrook; Robert Wise; Scott T. Weiss; Kathleen Barnes
• Keywords: SNP; Linkage Disequilibrium

Interpatient variability in montelukast response may be related to variation leukotriene pathway candidate genes.To determine associations between polymorphisms genes with outcomes patients asthma receiving for 6 mo who participated a clinical trial.Polymorphisms were typed using Sequenom matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass array spectrometry and published methods; haplotypes imputed single nucleotide polymorphism-expectation maximization (SNP-EM). Analysis of variance logistic regression models used test changes by genotype. In addition, chi(2) likelihood ratio tests differences groups. Case-control comparisons analyzed the SNP-EM Omnibus test.Outcomes exacerbation rate FEV(1) compared baseline.DNA was collected from 252 participants: 69% white, 26% African American. Twenty-eight SNPs ALOX5, LTA4H, LTC4S, MRP1, cysLT1R genes, an ALOX5 repeat polymorphism successfully typed. There racial disparities allele frequencies 17 polymorphism. Association analyses performed 61 whites. Associations found genotypes (rs2115819) MRP1 (rs119774) (p < 0.05), two LTC4S (rs730012) LTA4H (rs2660845) rates. Mutant associated decreased strong linkage disequilibrium SNPs. risk exacerbations found.Genetic contributes response.