Telleria Juan J, Blanco-Quiros Alfredo, Varillas David, Armentia Alicia, Fernandez-Carvajal Isabel, Jesus Alonso M, Diez Ignacio
Institute of Biology and Molecular Genetics (IBGM/CSIC), University of Valladolid, Valladolid, Spain.
Respir Med. 2008 Jun;102(6):857-61. doi: 10.1016/j.rmed.2008.01.011. Epub 2008 Mar 12.
It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported.
Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5).
Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment.
It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast.
有假设认为，白三烯途径存在突变等位基因的哮喘患者对白三烯受体拮抗剂不应产生反应，且越来越多的人支持个性化治疗的概念。
61例中度持续性哮喘患者（平均年龄24.9岁，范围14 - 52岁）在接受孟鲁司特6个月治疗前后进行了临床和免疫学评估。对5-脂氧合酶基因（ALOX5）启动子（-147至-176）中的串联重复多态性进行基因分型。
32例患者（52.5%）为5次重复等位基因纯合子；17例（27.9%）为杂合子（4/5次重复），12例（19.7%）为4/4次重复纯合子。孟鲁司特治疗后，5/5或4/5次重复的患者哮喘发作次数减少，第一秒用力呼气容积（FEV₁）改善，β₂激动剂使用减少。相反，4/4次重复基因型的患者治疗后这些数据没有改变。
证实了ALOX5启动子多态性对特应性中度持续性哮喘患者的孟鲁司特反应有明显影响。基因研究可以识别出最可能对孟鲁司特产生反应的患者。
