Objective: To investigate the frequencies of leukotriene gene single nucleotide polymorphisms (SNPs) in the asthmatic subjects of Han population in Wenzhou district, and the association between SNPs and response to montelukast treatment.
Methods: Sequenom matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) was used to genotype six polymorphisms in 60 asthmatic patients and 61 controls. According to the SNPs results, 11 cases with the LTC(4)S (rs730012) CC + AC genotype and 11subjects with the AA genotype were given montelukast treatment, and evaluated by the response of pulmonary function and urinary leukotriene E(4).
Results: The frequencies of mutant SNPs in ALOX(5) (rs2115819, rs4986832, rs4987105), LTA(4)H (rs2660845), ALOX(5)AP (rs10507391) and LTC(4)S (rs730012) were less than 50%. There were no statistical differences of the haplotype distribution (P values were 0.914, 0.609, 0.609, 0.315, 0.752 and 0.636 respectively). No statistical differences of the mutant allele frequencies were observed in the genes ALOX(5) (rs2115819, rs4986832, rs4987105) and LTA(4)H (rs2660845) (OR values were 1.112, 0.964, 0.964 and 0.673 respectively, all P > 0.05). The invalid value (OR = 1.0) was included in the 95%CI of odds ratios. There were no differences of genotype distribution in the above loci (χ(2) values were 0.792, 2.684, 2.683 and 2.524 respectively, all P > 0.05). There was a statistical difference in the ALOX(5)AP (rs10507391) mutant allele between the 2 groups, and the frequency of mutant allele A in the asthma group was 23.3% (OR = 2.016, 95%CI = 1.027 - 3.959, P < 0.05). There was a statistical difference in the LTC(4)S (rs730012) mutant allele between the 2 groups, and the frequency of the mutant allele C in the asthma group was 25.0% (OR = 1.926, 95%CI = 1.007 - 3.685, P < 0.05). Compared with the AA genotype, the LTC(4)S (rs730012) CC + AC genotype showed a significant improvement of FEV(1) (t = 6.185, P < 0.01) and urinary LTE(4) level (t = 2.925, P < 0.05) after receiving montelukast treatment.
Conclusions: These results suggest that the SNPs of ALOX(5)AP (rs10507391) and LTC(4)S (rs730012) are associated with asthma in our patients. The LTC(4)S (rs730012) locus genetic polymorphism contributes to improvement in montelukast response.