Leung Ting Fan, Tang Nelson L S, Sung Ying Man, Li Chung Yi, Ma Suk Ling, Lam Christopher W K, Wong Gary W K
Department of Paediatrics, The Chinese Univesity of Hong Kong, Prince of Wales Hospital, Hong Kong.
Pediatr Allergy Immunol. 2006 Nov;17(7):501-7. doi: 10.1111/j.1399-3038.2006.00446.x.
Mannose-binding lectin (MBL), a member of the innate immune system, initiates complement deposition on microbial surfaces. MBL deficiency is associated with severe respiratory infections. Polymorphisms in the MBL gene (mbl2) were associated with the susceptibility and severity of autoimmune diseases. This study investigated whether mbl2 polymorphisms at positions -550 and -221 and at codon-54 are associated with asthma phenotypes in Chinese children. Asthmatics aged 5-18 yr and non-allergic controls were eligible, and their plasma total and allergen-specific immunoglobulin E (IgE) concentrations were measured by micro-particle immunoassay and fluorescent enzyme immunoassay. mbl2 polymorphisms were genotyped by restriction fragment length polymorphism. Three hundred and seventeen asthmatic children and 140 controls were recruited, with their mean (s.d.) log-transformed plasma total IgE being 2.61 (0.61) and 1.77 (0.77), respectively (p < 0.0001). Polymorphisms at -550 and codon-54 (p < 0.0001 for both) but not at -221 (p = 0.534) of mbl2 were significantly associated with plasma MBL concentrations. mbl2 genotypes were not associated with asthma, atopy, sensitization to individual aeroallergens or spirometric variable. Subjects with LYB haplotype had the lowest plasma MBL concentrations (p < 0.0001), but two- and three-loci mbl2 haplotypes were also not associated with asthma diagnosis. However, patients with LY and LYB haplotypes were less likely to be atopic (p = 0.006 and 0.031). Subjects with LY and LYA were also less likely to be sensitized to cockroach (p = 0.035 and 0.047). The latter three associations became insignificant when adjusted for multiple comparisons. Despite the importance of MBL in innate immunity, our mbl2 polymorphisms only show weak association with asthma and atopy in children.
甘露糖结合凝集素（MBL）是先天性免疫系统的成员，可启动补体在微生物表面的沉积。MBL缺乏与严重的呼吸道感染有关。MBL基因（mbl2）的多态性与自身免疫性疾病的易感性和严重程度有关。本研究调查了mbl2基因-550位、-221位和54密码子处的多态性是否与中国儿童的哮喘表型相关。纳入年龄在5至18岁的哮喘患者和非过敏对照，通过微粒免疫测定法和荧光酶免疫测定法测量他们血浆中的总免疫球蛋白E（IgE）和过敏原特异性IgE浓度。通过限制性片段长度多态性对mbl2基因多态性进行基因分型。招募了317名哮喘儿童和140名对照，他们经对数转换后的血浆总IgE均值（标准差）分别为2.61（0.61）和1.77（0.77）（p<0.0001）。mbl2基因-550位和54密码子处（两者p均<0.0001）而非-221位（p=0.534）的多态性与血浆MBL浓度显著相关。mbl2基因分型与哮喘、特应性、对个体气传过敏原的致敏或肺功能变量无关。具有LYB单倍型的受试者血浆MBL浓度最低（p<0.0001），但双位点和三位点mbl2单倍型也与哮喘诊断无关。然而，具有LY和LYB单倍型的患者发生特应性的可能性较小（p=0.006和0.031）。具有LY和LYA单倍型的受试者对蟑螂致敏的可能性也较小（p=0.035和0.047）。在进行多重比较校正后，后三种关联变得不显著。尽管MBL在先天性免疫中很重要，但我们研究的mbl2基因多态性仅显示与儿童哮喘和特应性有弱关联。
