Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility
Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility
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DOI：
10.1111/j.1365-2222.2006.02413.x
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发表时间：
2006-07-01
影响因子：
6.1
通讯作者：
Nishimura, M.
中科院分区：
文献类型：
--
作者：
Hizawa, N.;Maeda, Y.;Nishimura, M.
背景我们先前在日本人群中检测到IgE高亲和力受体β链（FCER 1B）基因启动子多态性（-109C/T），该多态性与总血清IgE水平相关，但与哮喘无关。在生物学上，Fc β 2受体抑制剂-β和纤溶酶原激活物抑制剂1（派-1）之间可能存在遗传相互作用，PAI-1在哮喘患者的肥大细胞中高度表达，并在气道重塑中起重要作用。我们假设FCER 1B启动子多态性通过改变肥大细胞激活信号的强度，目的探讨派-1基因FCER 1B启动子区多态性对哮喘发病的影响（-109C/T和-654C/T）影响派-1基因功能多态性（4G/5G）的遗传效应。方法根据FCER 1B-109 TT和-654 CC基因型及派-1 4G等位基因的存在情况，将374例哮喘患者和374例非哮喘对照者分为联合基因型组。结果FCER 1B-109 T/-654C单倍型和派-1 5G等位基因纯合子个体发生哮喘的易感性降低，发生哮喘的OR值为0.20（95%置信区间，0.084-0.46; P=0.00015），与FCER 1B的-109T/-654C单倍型纯合但派-1携带4G等位基因的个体相比。派-1 4G/5G基因型与FCER 1B-109 C/T（P =0.0017）和FCER 1B-654 C/T（P =0.031）基因型在哮喘发病中存在交互作用。
Background We previously detected a promoter polymorphism (-109C/T) in the gene for the beta-chain of the high-affinity receptor for IgE (FCER1B), which was associated with total serum IgE levels but not with asthma in a Japanese population. A genetic interaction is biologically plausible between Fc epsilon RI-beta and the plasminogen activator inhibitor 1 (PAI-1), which is highly expressed in mast cells in asthmatics and plays an essential role in airway remodelling. We hypothesized that FCER1B promoter polymorphisms, by modifying the intensity of mast cell activation signals, modulate the genetic effects of a functional 4G/5G polymorphism in the PAI-1 gene on asthma.Objective To examine whether FCER1B promoter polymorphisms (-109C/T and -654C/T) influence the genetic effects of the functional polymorphism (4G/5G) at the PAI-1 promoter region on asthma susceptibility using a case-control analysis.Methods Subjects (374 asthmatic patients and 374 non-asthmatic controls) were divided into combined genotype groups based on the presence of FCER1B-109TT and -654CC genotypes and the PAI-1 4G allele. Logistic regression analysis was used to estimate adjusted odds ratios for asthma associated with the different genotype groups.Results Individuals homozygous for the FCER1B-109T/-654C haplotype and the PAI-1 5G allele had a reduced susceptibility to asthma; the odds ratio for the development of asthma was 0.20 (95% confidence interval, 0.084-0.46; P=0.00015) for them, compared with individuals also homozygous for the -109T/-654C haplotype at FCER1B but carrying the 4G allele at PAI-1. The regression model also showed an interaction of the PAI-1 4G/5G genotype with the FCER1B-109C/T (P for interaction=0.0017) or FCER1B-654C/T (P for interaction=0.031) on asthma.Conclusions The present findings suggest a synergistic interaction between FCER1B and PAI-1 genes in asthma susceptibility.