Guerra Stefano, Graves Penelope E, Morgan Wayne J, Sherrill Duane L, Holberg Catharine J, Wright Anne L, Martinez Fernando D
Arizona Respiratory Center, University of Arizona, 1501 N Campbell Ave, PO Box 245030, Tucson, AZ 85724-5030, USA.
Chest. 2005 Aug;128(2):609-17. doi: 10.1378/chest.128.2.609.
It has long been recognized that many children with asthma outgrow the disease after the onset of puberty, but little is known about genetic factors influencing this outcome.
The aim of the present study was to determine whether the polymorphisms at codons 16 and 27 of the beta2-adrenoceptor are significant predictors of the persistence of asthma during adolescence.
We used data from the prospective Tucson Children's Respiratory Study. Children were genotyped for the polymorphisms at codons 16 and 27. The presence of wheezing/asthma was assessed by questionnaire from age 6 years up to the reported onset of puberty (prepubertal period) and after the onset of puberty up to age 16 years (adolescence).
Among children who wheezed in the prepubertal period (n = 168), subjects homozygous for Gly at codon 16 were at significantly increased risk for persistent wheezing after puberty, as compared with carriers of the other genotypes (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06 to 1.92; p = 0.019). This relation was present among boys (RR, 2.17; 95% CI, 1.41 to 3.36) but not girls (RR, 0.85; 95% CI, 0.55 to 1.30), and increased linearly according to the frequency of wheezing episodes after the onset of puberty. These findings persisted after adjusting for ethnicity and other potential confounders and after selecting only white children. The polymorphism at codon 27 showed no relation with risk for persistent wheezing.
This study provides evidence for a strong gender-specific effect of the Gly16 polymorphism on the persistence of asthma after the onset of puberty.
长期以来人们认识到，许多哮喘儿童在青春期开始后会摆脱该疾病，但对于影响这一结果的遗传因素知之甚少。
本研究的目的是确定β2肾上腺素能受体第16和27密码子的多态性是否是青春期哮喘持续存在的重要预测指标。
我们使用了来自图森儿童呼吸研究的前瞻性数据。对儿童进行第16和27密码子多态性的基因分型。通过问卷评估6岁至报告的青春期开始（青春期前）以及青春期开始至16岁（青春期）期间喘息/哮喘的存在情况。
在青春期前喘息的儿童（n = 168）中，与其他基因型携带者相比，第16密码子纯合甘氨酸的受试者青春期后持续喘息的风险显著增加（相对风险[RR]，1.43；95%置信区间[CI]，1.06至1.92；p = 0.019）。这种关系在男孩中存在（RR，2.17；95%CI，1.41至3.36），但在女孩中不存在（RR，0.85；95%CI，0.55至1.30），并且根据青春期开始后喘息发作的频率呈线性增加。在调整种族和其他潜在混杂因素后以及仅选择白人儿童后，这些发现仍然存在。第27密码子的多态性与持续喘息的风险无关。
本研究为甘氨酸16多态性对青春期后哮喘持续存在的强烈性别特异性影响提供了证据。
