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支气管哮喘患者白三烯基因多态性与抗白三烯治疗的相关性研究 被引量:14

Association of leukotriene gene polymorphisms with response to antileukotriene treatment in patientswith asthma
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摘要 目的检测温州地区汉族人支气管哮喘(简称哮喘)患者白三烯酶基因多态性的分布频率,探讨酶基因多态性与孟鲁司特治疗的相关性。方法采用基质辅助激光解吸附电离飞行时间质谱法,对60例温州汉族哮喘患者(哮喘组)及61名健康者(对照组)的6个白三烯酶基因多态性位点进行检测。依据基因检测结果选取基因白三烯C4 合成酶LTC4S(rs730012)CC+AC型11例与AA型11例,观察孟鲁司特治疗4周后的肺功能和尿白三烯E4的变化。结果(1)6个基因位点[5脂氧酶ALOX,(rs2115819、rs4986832、rs4987105)、白三烯A。水解酶LTA4H(rs2660845)、5脂氧酶结合蛋白ALOX,AP(rsl0507391)和LTC。S(rs730012)]的变异频率均〈50%,单体型组间分布差异均无统计学意义(均P〉0.05)。(2)基因ALOX;(rs2115819、rs4986832、rs4987105)和LTA。H(rs2660845)等位点变异等位基因频率组间比较差异均无统计学意义(OR值分别为1.112、0.964、0.964、0.673,均P〉0.05),变异等位基因OR值95%可信区间(95%C/)均包括无效值(OR=1.0)。上述位点基因型组间比较差异均无统计学意义(X^2值分别为0.792、2.684、2.683、2.524,均P〉0.05)。(3)基因ALOX,AP(rsl0507391)位点在两组间存在差异,哮喘组变异等位基因A频率为23.3%(OR=2.016,95%C,为1.027~3.959,P〈0.05)。基因LTC。S(rs730012)位点在两组间存在差异,哮喘组变异等位基因c频率为25.0%(OR=1.926,95%C/为1.007~3.685,P〈0.05)。(4)孟鲁司特治疗4周后,基因LTC。S(rs730012)CC+AC型者的FEVl提高(t=6.185,P〈0.01),晨尿LTE4下降(t=2.925,P〈0.05)。AA型者治疗前后的FEV,和LTE。无明显变化。结论温州地区汉族人群中基因ALOX5AP(rs10507391)、LTC4S(rs730012)位点的变异与哮喘相关,而另外4个位点的变异与哮喘无关。携带LTC4S(rs730012)变异等位基因c型可影响孟鲁司特的治疗效应。 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 LTCaS (rs730012) CC + AC genotype and l lsubjects with the AA genotype were given montelukast treatment, and evaluated by the response of pulmonary function and urinary leukotriene E4. Results The frequencies of mutant SNPs in ALOX5 ( rs2115819, rs4986832, rs4987105 ), LTA4H ( rs2660845 ), ALOXsAP ( rs10507391 ) and LTCgS (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 ALOX5 (rs2115819, rs4986832, rs4987105) and LTA4H (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 ( X2 values were 0. 792, 2. 684, 2. 683 and 2. 524 respectively, all P 〉 0. 05).There was a statistical difference in the ALOXsAP (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 LTC4 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 LTC4S (rs730012) CC + AC genotype showed a significant improvement of FEV~ (t =6. 185, P 〈0. 01 ) and urinary LTE4 level (t =2. 925, P 〈0. 05) after receiving montelukast treatment. Conclusions These results suggest that the SNPs of ALOXsAP (rs10507391) and LTC4S(rs730012) are associated with asthma in our patients. The LTC4S(rs730012) locus genetic polymorphism contributes to improvement in montelukast response.
出处 《中华结核和呼吸杂志》 CAS CSCD 北大核心 2011年第5期362-366,共5页 Chinese Journal of Tuberculosis and Respiratory Diseases
基金 基金项目:2008年度浙江省自然科学基金(Y2080192)
关键词 哮喘 白三烯类 多态性 单核苷酸 孟鲁司特 Asthma Leukotrienes Polymorphism, single nucleotide Montelukast
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参考文献14

  • 1Montusehi P, Peters-Golden ML. Leukotriene modifiers for asthma treatment. Clin Exp Allergy, 2010,40:1732-1741.
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二级参考文献2

  • 1Quanjer PH, Tammeling CJ, Cotes JE,et al. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests,European Community for Steel and Coal. Eur Respir J, 1993,6 Suppl: 5-40.
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