ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma.
ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma.
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DOI：
10.1111/cea.12076
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Lima JJ
中科院分区：
文献类型：
--
作者：
Mougey E;Lang JE;Allayee H;Teague WG;Dozor AJ;Wise RA;Lima JJ
确定哮喘控制降低的危险因素可以提高对哮喘的认识和治疗。5-脂氧合酶基因的启动子多态性影响基因表达和对哮喘治疗的反应，但其对疾病控制的影响尚不清楚。我们试图确定ALOX5启动子SP1串联重复多态性是否与半胱氨酸白三烯生成、肺功能、气道炎症和哮喘控制评分的变化有关。我们分析了270名6-17岁哮喘控制不良的儿童，他们参加了一项为期6个月的临床试验（NCT00604851）。在二级分析中，我们使用加性和隐性遗传模型将ALOX5启动子SP1串联重复多态性基因型（rs59439148）与哮喘结局联系起来。我们评估了预测fev1%、症状控制、呼出一氧化氮和尿LTE4水平。14.8%的儿童（40/270）和28%的非裔美国人（38/135）携带rs59439148的2个非5重复变异等位基因。变异等位基因纯合子的儿童尿LTE4水平显著较高（38对30 nmol/mol肌酐，p= 0.0134），预测的FEV1%显著较差（84对91，p= 0.017），并且哮喘控制有较差的趋势。FEV1%预测值与尿LTE4呈显著负相关（r = -0.192, p= 0.009）。携带两个小变异ALOX5启动子SP1串联重复等位基因的拷贝会增加尿LTE4水平，降低肺功能，并可能使哮喘控制恶化。ALOX5启动子SP1串联重复基因型可能是哮喘预后恶化的危险因素。
Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy but its impact on disease control remains unclear. We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score. We analyzed 270 children 6-17 years old with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels. 14.8% (40/270) of all children (and 28% (38/135) of African Americans) carried 2 non-5 repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 versus 30 nmol/mol creatinine, p=.0134), significantly worse FEV1% predicted (84 versus 91, p=.017), and a trend toward worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = -0.192, p=.009). Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function, and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.
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影响因子：
8
作者：
Akinbami, LJ;Rhodes, JC;Lara, M
通讯作者：
Lara, M
DOI：
10.1164/rccm.200406-710st
发表时间：
2005-04-15
影响因子：
24.7
作者：
American Thoracic Society;European Respiratory Society
通讯作者：
European Respiratory Society
影响因子：
8
作者：
Akinbami, Lara J.;Moorman, Jeanne E.;Sondik, Edward J.
通讯作者：
Sondik, Edward J.
5-脂氧合酶和5-脂氧合酶激活蛋白定位于活化的人白细胞的核包膜中。
DOI：
10.1084/jem.178.6.1935
发表时间：
1993-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Woods JW;Evans JF;Ethier D;Scott S;Vickers PJ;Hearn L;Heibein JA;Charleson S;Singer II
通讯作者：
Singer II
影响因子：
2.6
作者：
Rabinovitch, Nathan
通讯作者：
Rabinovitch, Nathan