燃煤型室内空气污染物与儿童哮喘易感基因的关系研究

Association between indoor coal-burning pollutants associated with asthmatic susceptible genetic polymorphisms in childhood asthma

目的了解贵州省贵定县哮喘儿童居室内燃煤型空气污染物(PM4、SO2、CO)的暴露水平和哮喘儿童中β2肾上腺素能受体(β2-AR)基因第16、27位点以及血管紧张素转移酶(ACE)基因的分布频率,揭示燃煤型空气污染物和哮喘易感基因的交互作用与儿童哮喘发病风险的关系。方法采用单纯病例研究的流行病学方法,通过PCR方法检测231个哮喘患儿的β2肾上腺素能受体(β2-AR)基因第16、27位点多态性和血管紧张素转移酶(ACE)基因插入/缺失(I/D)多态性以及哮喘儿童家庭居室内空气中PM4、SO2、CO的浓度,计算两种哮喘易感基因多态性的分布频率,并判断PM4、SO2、CO与β2-AR基因第16、27位点多态性以及血管紧张素转移酶(ACE)基因插入/缺失(I/D)多态性在儿童哮喘的发生中是否存在相乘模型的交互作用。结果哮喘儿童的燃煤型空气污染物暴露率为87.4%(202人);β2-AR基因16位点Arg/Arg纯合子、Gly/Gly纯合子、Arg/Gly杂合子在哮喘儿童中的分布频率分别为13.9%、13.4%和72.7%;27位点Gln/Gln纯合子、Glu/Glu纯合子、Gln/Glu杂合子的频率分别为13.9%、4.3%和81.8%,ACE基因Ⅱ、DD和ID基因型的频率分别为49.3%、20.0%和30.7%。PM4、SO2、CO和β2-AR基因多态性以及ACE基因多态性在儿童哮喘的发生中存在相乘模型的交互作用(均P<0.05)。结论当地乡村燃煤型室内空气污染问题较为突出;三种哮喘易感基因多态性的频率分布在当地有一定特殊性;煤型空气污染物(PM4、SO2、CO)与β2-AR基因16位点Gly/Gly基因型和ACE基因DD基因型的交互作用可能增加儿童哮喘发生的危险性。

Objective To determine the level of exposure to indoor pollutants （PM4 , SO2, CO） produced by burning coal in home of asthmatic children in Guiding County, Guizhou Province, and to observe the distribution frequencies of ACE gene and the 16th and 27th loci of β2 adrenergic receptor （β2-AR） gene in the children, and to reveal the association between the pollutants and the susceptible genes in childhood asthma. Methods Case-only study, an epidemiologic method, was employed. PCR was used to examine the polymorphisms at the 16th and 27th loci of β2-AR gene and the insertion/deletion （I/D） polymorphisms of angiotensin converting enzyme （ACE） gene in 231 children suffered from asthma. PM4, SO2 and CO concentrations of indoor air in the children＇s homes were measured. The distribution frequencies of the polymorphisms were calculated. And the possible interaction of multiplication model between the pollutants and the polymorphisms was determined. Results Rate of exposure to coal-burning air pollutants was 87.4% （202 children） among the children suffered from asthma. The distribution frequencies of the Arg/Arg and Gly/Gly homozygotes and the Arg/Gly heterozygote at the 16th locus of β2-AR gene were 13.9%, 13.4% and 72.7%, respectively, and the frequencies of the Gln/Gln and Glu/Glu homozygotes and the Glu/Glu heterozygote at the 27th locus were 13.9% , 4.3% and 81.8% , respectively, and the frequencies of the Ⅱ, DD and ID genotypes of ACE gene were 49.3%, 20.0% and 30.7%, respectively; and an interaction of multiplication model could exist between the air pollutants, PM4 , SO2 , and CO, and the β2-AR and ACE polymorphisms for the occurrence of childhood asthma （ P 〈 0.05 for all indicators） . Conclusion The problem of air pollution from burning coal maybe serious in the local rural area. The distribution frequencies of the three susceptible polymorphisms for asthma could have their individual characteristics. And the air pollutants, PM4, SO2 and CO, interacted with the Gly/Gly genotype at the 16th locus of β2-AR gene or the DD genotype of ACE gene maybe increases the risk for asthma in children.