重新认识β2受体基因多态性与哮喘的关系
2007/03/09
Hall等进行的英国1958出生群组研究是首个有充足效力的研究，该研究对八千余名1958年3月3日-9日出生的英国新生儿进行了为期45年的随访，分别在7岁，11岁，16岁，23岁，33岁，42岁时接受随访，由医生诊断是否患有哮喘，喘息性支气管炎或喘息，在35岁及45岁时分别测定肺功能，45岁时提取8018名受试者的DNA，测定ADRB2三个编码区的基因型，并将哮喘患病率，预后，肺功能与ADRB2基因多态性进行关联研究。结果发现与全程随访中哮喘患病率及发病年龄均与ADRB2无关，仅Arg16Gly与Gln27Glu与哮喘症状是否从儿童时期持续到成年相关。Arg16Gly基因型的儿童哮喘患者中19.3%在42岁前一年中有超过5次喘息发作，而无此基因型者中此比例仅占11.9%。
作者认为此研究不支持此前Meta分析结果，ADRB2基因多态性仅是儿童哮喘长期预后很弱的预测因子，并非哮喘发病或患病率的重要决定因素。目前数以百计的哮喘基因研究表明多种通路参与哮喘的发病，但都不是决定因素。
β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study.
Authors: LP Hall, JD Blakey, KA Al Balushi, et al.
Source: Lancet; 368(9537):771-779. 2005，
Abstract: Summary Background Functionally relevant polymorphisms of the β2-adrenoceptor gene (ADRB2) are common in white populations, but their contribution to the burden of airways disease in the population is uncertain. We aimed to relate the long-term prevalence of asthma or wheeze to functional coding region polymorphisms in the ADRB2 gene.
Methods The British 1958 birth cohort consisted of all people born in Britain during a week in 1958. Asthma, wheezy bronchitis, and wheezing were ascertained by interview at ages 7, 11, 16, 23, 33, and 42 years, and lung function tests at 35 and 45 years. DNA samples from 8018 participants in the 45-year follow-up were genotyped for three coding variants in the ADRB2 gene. We extend the follow-up of this nationwide cohort by a further 10 years and relate asthma prevalence, prognosis, and lung function to functional coding region polymorphisms in the ADRB2 gene in the cohort members who contributed DNA samples. We also compared and combined our findings with those reaching significance in two previous meta-analyses.
Findings Half the cohort (4105 of 8018) had some history of wheezing illness by age 42 years. Neither lifetime prevalence nor age at onset were related to ADRB2 coding variants. However, the common polymorphisms Arg16Gly (rs1042713, Arg 16 allele frequency 36.3%) and Gln27Glu (rs1042714, Glu 27 allele frequency 44.6%) were significantly associated with persistence of asthmatic symptoms from childhood to middle age. Among homozygotes for the Arg16-Gln27 haplotype at these loci, 19.3% (41 of 212) childhood wheezers had five or more wheezing episodes in the past year at age 42, compared with 11.9% (71 of 599) with no copy of this haplotype. However, only 3% of all frequent adult wheezing was statistically attributable to this haplotype. The less common Thr164Ile polymorphism (rs1800888, Ile allele frequency 1.5%) was not a major predictor of either frequency or prognosis of asthma.
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诱导型一氧化氮合酶与哮喘严重性、血清总IgE及外周血嗜酸性粒细胞水平间的相关性研究
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先天免疫激活在中性粒细胞性哮喘及支气管扩张中的作用
