Genetic polymorphisms in arginase I and II and childhood asthma and atopy
Genetic polymorphisms in arginase I and II and childhood asthma and atopy
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DOI：
10.1016/j.jaci.2005.09.026
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发表时间：
2006-01-01
影响因子：
14.2
通讯作者：
London, SJ
中科院分区：
文献类型：
--
作者：
Li, HL;Romieu, I;London, SJ
背景：最近的一项微阵列研究表明，精氨酸酶I （ARGI）和精氨酸酶II （ARG2）与小鼠过敏性哮喘模型和人类哮喘有关。目的：探讨ARGI和ARG2基因变异与儿童哮喘和特应性风险的关系。方法：1998年至2003年，我们从墨西哥城一家公立医院的过敏诊所招募了433例病例-父母三联组，包括4至17岁的哮喘患者及其亲生父母。皮肤点刺试验测定24种空气过敏原的特应性。我们使用TaqMan法（Roche Molecular Systems, Pleasanton, Calif .）对ARG1的4个单核苷酸多态性（SNPs）和ARG2的4个小等位基因频率高于10%的snp进行了基因分型。结果：ARGI snp和单倍型与哮喘无关，但所有4个ARGI snp均与皮肤试验阳性次数相关（P = 0.007 - 0.018）。携带2个高度相关ARG2 snp的次要等位基因拷贝与哮喘相对风险（RR）增加有统计学意义（arg2s1为1.5,95% CI = 1.1-2.1； arg2s2为1.6,95% CI = 1.1-2.3）相关。在父母吸烟的儿童中，相关性略强（arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9; RR = 1.2, 95% CI = 0.8-1.9；交互作用P = 0.025）。单倍型分析减少了样本量，但支持单SNP结果。1个ARG2 SNP与皮肤试验阳性次数相关（P = 0.027）。
Background: A recent microarray study implicated arginase I (ARGI) and arginase II (ARG2) in mouse allergic asthma models and human asthma.Objectives: To examine the association between genetic variation in ARGI and ARG2 and childhood asthma and atopy risk.Methods: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif).Results: ARGI SNPs and haplotypes were not associated with asthma, but all 4 ARGI SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027).