Mak Judith C W, Ko Fanny W S, Chu Chung M, Leung Helen C M, Chan Henry W, Cheung Amy H K, Ip Mary S M, Chan-Yeung Moira
Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
Int Arch Allergy Immunol. 2007;144(2):114-22. doi: 10.1159/000103222. Epub 2007 May 24.
Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. However, association studies with interleukin-4 (IL-4), IL-4 receptor alpha subunit (IL-4R alpha), tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were inconclusive, as both positive and negative results were obtained in several populations studied. We aimed to investigate the association of the polymorphisms for IL-4 (C-589T), IL-4R alpha (Gln576Arg), TNF-alpha (G-308A) and LT-alpha (A252G) genes as candidates and asthma in adult Hong Kong Chinese population.
The association study was conducted in an age- and smoking status-matched case-control design in asthma patients (n = 292) and healthy controls (n = 292) using polymerase chain reaction and restriction fragment length polymorphism.
No significant differences were found in allele and genotype frequencies of all four genes between patients and controls. After stratification by atopic status, the heterozygous AG genotype of LT-alpha (A252G) was found to increase risk of asthma in atopic population [odds ratio (OR) = 2.00, 95% CI 1.09-3.67, p = 0.024]. When stratified by smoking status, we found increased risk of asthma with subjects carrying the heterozygous AG and homozygous GG genotypes of LT-alpha in ever-smokers (OR = 2.73, 95% CI 1.11-6.69, p = 0.028 for heterozygotes; OR = 3.34, 95% CI 1.16-9.62, p = 0.026 for homozygotes).
Our results suggest that the variability of LT-alpha genotypes may have potential implications for individual susceptibility to asthma in atopic or in ever-smoking Chinese adults in Hong Kong.
已知哮喘和其他特应性疾病的易感性与遗传因素有关。然而,对白介素-4(IL-4)、IL-4受体α亚基(IL-4Rα)、肿瘤坏死因子-α(TNF-α)和淋巴毒素-α(LT-α)基因的关联研究尚无定论,因为在多个研究人群中均得到了阳性和阴性结果。我们旨在研究作为候选基因的IL-4(C-589T)、IL-4Rα(Gln576Arg)、TNF-α(G-308A)和LT-α(A252G)基因多态性与成年香港华人哮喘的关联。
采用年龄和吸烟状况匹配的病例对照设计,对哮喘患者(n = 292)和健康对照者(n = 292)进行关联研究,使用聚合酶链反应和限制性片段长度多态性技术。
患者和对照者中所有四个基因的等位基因和基因型频率均无显著差异。按特应性状态分层后,发现LT-α(A252G)的杂合AG基因型增加了特应性人群患哮喘的风险[比值比(OR)= 2.00,95%可信区间1.09 - 3.67,p = 0.024]。按吸烟状况分层时,我们发现曾经吸烟者中携带LT-α杂合AG和纯合GG基因型的受试者患哮喘的风险增加(杂合子OR = 2.73,95%可信区间1.11 - 6.69,p = 0.028;纯合子OR = 3.34,95%可信区间1.16 - 9.62,p = 0.026)。
我们的结果表明,LT-α基因型的变异性可能对香港特应性或曾经吸烟的中国成年人个体患哮喘的易感性具有潜在影响。