WONCA研究论文摘要汇编——GLCCI1与糖皮质激素哮喘疗法反应的基因组相关

发布时间：2018-02-04 07:48

本文关键词： 治疗反应遗传药理学吸入性糖皮质激素受试者糖皮质激素反应相关性变异体哮喘混合数据等位基因　出处：《中国全科医学》2011年36期 　论文类型：期刊论文

【摘要】：背景哮喘治疗反应个体间差异显著,且有相当数目病人无治疗反应。假设全基因组相关研究将揭示吸入性皮质激素反应新遗传药理学决定子。方法以家庭筛查算法为基础,从534 290单核苷酸多态性(single-nucleotide polymorphisms,SNPs)中挑选有统计学效力小数目变异体进行分析,以确定吸入皮质激素治疗反应的肺功能变化。发现了一种显著、重复的相关性,我们对其功能效应做特征化描述。结果在SNP rs37972识别出一种有显著遗传药理学相关,此相关4个独立人群含935人重复出现(P=0.0007),即基因图谱中对糖皮质激素诱导的转录基因1(GLCCI1),定位rs37973完全连锁不平衡(如完整的交互关系)。rs37972和rs37973两者均与GLCCI1表达减少相关。在分离细胞系统中,rs37973变异体与荧光素酶指示器活动度明显减小相关。治疗试验的混合数据表明,等位基因变异受试者对吸入性糖皮质激素肺反应功能下降(混合数据P=0.0007)。总体,接受治疗受试者中,突变rs37973等位基因纯合子者一秒用力呼气量平均增加仅是接受相同治疗野生型等位基因受试者的1/3[(3.2±1.6)%与(9.4±1.1%)],且其不良风险明显要高[OR=2.36,95%CI(1.27,4.41)],基因型占总吸入性糖皮质激素反应变异性的6.6%。结论功能性GLCCI1变异体与哮喘病人对吸入性糖皮质激素的反应明显下降相关。
[Abstract]:Background there are significant differences among individuals in the treatment of asthma. Assuming that genome-wide studies will reveal new genetic pharmacokinetic determinants of inhaled corticosteroid response, the method is based on a family screening algorithm. Single nucleotide polymorphisms from 534 290 single nucleotide polymorphisms. A small number of statistically potent variants were selected for analysis to determine changes in lung function in response to inhaled corticosteroid therapy. A significant and repeated correlation was found. The functional effects were characterized. Results A significant genetic pharmacological correlation was identified in SNP rs37972. There were 935 individuals in the four independent population who had repeated occurrence of PX 0.0007, i.e. glucocorticoid-induced transcriptional gene (GLCCI1) in the gene map. The localization of complete linkage disequilibrium of rs37973 (such as complete interaction. Rs37972 and rs37973 are both associated with reduced expression of GLCCI1.) in the isolated cell system. Rs37973 variants were significantly associated with decreased luciferase indicator activity. Allelic variation in subjects with reduced pulmonary response to inhaled glucocorticoids (mixed data P0. 0007). Overall, in subjects receiving treatment. The 1 second forced expiratory volume in homozygous mutant rs37973 alleles increased by an average of only 1/3 of those receiving the same treatment for wild type alleles. [(3.2 卤1.6% vs 9.4 卤1.1), and the risk of adverse effects was significantly higher. [OR2.36 / 95 CIQ 1.27 / 4.41). Genotypes accounted for 6.6% of the total inhaled glucocorticoid response variability. Conclusion functional GLCCI1 variants are associated with a significantly decreased response to inhaled glucocorticoid in asthmatic patients.
【作者单位】：中国石油中心医院;
【分类号】：R562.25
【正文快照】： 原文见:Tantisira KG,Lasky-Su J,Harada M,et al.Genomewide association between GLCCI1 and response to glucocorticoid thera-py in asthma[J].New England Journal of Medicine,2011,365:1173-1183.Published at http://www.globalfamilydoctor.com/search/GFDSearch.as

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