Cai Chang, Zhou Mei-xi, Li Yu-ping, Chen Cheng-shui
Department of Respiratory Medicine, the First Hospital Affiliated to Wenzhou Medical College, Wenzhou 325000, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2011 May;34(5):362-6.
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.
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).
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.
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.
研究温州地区汉族哮喘患者白三烯基因单核苷酸多态性（SNP）的频率，以及SNP与孟鲁司特治疗反应之间的关联。
采用Sequenom基质辅助激光解吸/电离飞行时间（MALDI-TOF）技术对60例哮喘患者和61例对照者的6种多态性进行基因分型。根据SNP结果，对11例LTC(4)S（rs730012）CC + AC基因型患者和11例AA基因型患者给予孟鲁司特治疗，并通过肺功能和尿白三烯E(4)反应进行评估。
ALOX(5)（rs2115819、rs4986832、rs4987105）、LTA(4)H（rs2660845）、ALOX(5)AP（rs10507391）和LTC(4)S（rs730012）中突变SNP的频率均低于50%。单倍型分布无统计学差异（P值分别为0.914、0.609、0.609、0.315、0.752和0.636）。在ALOX(5)（rs2115819、rs4986832、rs4987105）和LTA(4)H（rs2660845）基因中，未观察到突变等位基因频率的统计学差异（OR值分别为1.112、0.964、0.964和0.673，均P>0.05）。优势比的95%CI包含无效值（OR = 1.0）。上述位点的基因型分布无差异（χ(2)值分别为0.792、2.684、2.683和2.524，均P>0.05）。两组间ALOX(5)AP（rs10507391）突变等位基因存在统计学差异，哮喘组突变等位基因A的频率为23.3%（OR = 2.016，95%CI = 1.027 - 3.959，P < 0.05）。两组间LTC(4)S（rs730012）突变等位基因存在统计学差异，哮喘组突变等位基因C的频率为25.0%（OR = 1.926，95%CI = 1.007 - 3.685，P < 0.05）。与AA基因型相比，LTC(4)S（rs730012）CC + AC基因型在接受孟鲁司特治疗后，FEV(1)（t = 6.185，P < 0.01）和尿LTE(4)水平（t = 2.925，P < 0.05）有显著改善。
这些结果表明，ALOX(5)AP（rs10507391）和LTC(4)S（rs730012）的SNP与我们研究中的患者哮喘相关。LTC(4)S（rs730012）位点基因多态性有助于改善孟鲁司特反应。
