Influence of Leukotriene Pathway Polymorphisms (Arachidonate 5-lipoxygenase ALOX5,Cysteinyl Leukotriene Receptor CysLTR1) On Response to Montelukast in A sample of Asthmatic Iraqi Patients

Abstract

Background: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe drug used in asthmatic patients. The mechanisms underlying the variation in response to montelukast are thought to be due to genetic variability partly. Objective: examine the genotype and allele frequencies of LT pathway candidate gene polymorphisms in Iraqi general population and asthmatic patients and determine associations between the genetic variants with outcomes in Iraqi patients with asthma receiving montelukast.
Method: This study conducted in a study group of Iraqi patients and healthy subjects from Baghdad. (200) participants (men, women)
recruited as healthy subjects (80) and patients with bronchial asthma (120) fulfill entry criteria and classified into three groups, first group contained 40 asthmatic patients taking montelukast for 4 weeks at a dose of 10 mg once a day before bed time, second group contained 40 asthmatic patients taking inhaled short acting beta agonist salbutamol at a dose of four buffs daily (0.1mg/dose) for 4 weeks, third group contain 40 asthmatic patients taking budesonide/formoterol inhalation powder(160/4.5mcg/dose) at a dose of two buffs daily for 4 weeks. Results: The allelic varients of ALOX5 and CysLTR1 were found in Iraqi population. G allele frequency of ALOX5(rs2115819) was (0.40), C allele frequency of CYSTL1 (rs320995) was (0.28) among the studied patients. C allele frequency of CysLTR1 for healthy individuals was (0.28) and G allele frequency of ALOX5(rs2115819) was (0.21) for healthy individuals. For ALOX5 SNP and CysLTR1 SNP in patients used montelukast, there was non-significant difference in percentage change in % predicted FEV1 over baseline and percentage change in % predicted PEF over baseline in patients taking montelukast. For salbutamol patients group, there was non-significant difference in percentage change in % predicted FEV1 over baseline for ALOX5 SNP and CysLTR1 SNP. For budesonide/formoterol inhalation powder patients group, non-significant difference in percentage change in % predicted FEV1 over baseline for ALOX5 SNP and CysLTR1 SNP. Conclusion: Our study results concluded that genetic variation in leukotriene pathway candidate genes may not contributed to variability in clinical responses to montelukast in Iraqi asthmatic patients from Baghdad who received montelukast for one month.