Hsieh Yao-Yuan, Wan Lei, Chang Chi-Chen, Tsai Chang-Hai, Tsai Fuu-Jen
1. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Int J Biol Sci. 2009;5(1):74-81. doi: 10.7150/ijbs.5.74. Epub 2009 Jan 9.
Asthma is caused by a complex interaction between multiple genes and environmental factors. Herein we aimed to investigate whether signal transducer and activator of transcription (STAT2), toll-like receptors 4 (TLRs4) and CD40-related polymorphisms are associated with asthma susceptibility.
Children were divided: (1) asthma (n=117); (2) normal controls (n=60). The polymorphisms of STAT2, TLR4 and CD40 polymorphism were analyzed by PCR-RFLP genotyping. Genotypes, allelic frequencies and association of haplotypes in both groups were compared.
STAT2C related genotypes, but not TLR4 and CD40 polymorphism, are associated with higher susceptibility for asthma. Distributions of STAT2CC/CG/GG and C/G allele in both groups are: (1) 0/11.1/88.9 % and 5.6/94.4%; (2) 0/1.7/98.3% and 0.8/99.2% (p<0.05). Proportions of TLR4rs10983755 AA/AG/GG and rs1927914 CC/CT/TT homozygote are: (1) 35.1/8.5/56.4% and 9.4/56.4/34.2%; (2) 35/8.3/56.7% and 16.7/48.3/35% (non-difference). Proportions of CD40rs1883832 CC/CT/TT, rs3765459 AA/AG/GG, and rs4810485 TT/GT/GG are: (1) 29.9/53/17.1%, 6.8/47.9/45.3 and 18.8/62.4/18.8%; (2) 36.7/41.7/21.6%, 1.6/46.7/ 51.7 and 15/51.7/33.3% (non-difference). Haplotype analyses for TLR4 and CD40 genes revealed their non-association and non-additional effect upon asthma susceptibilities.
STAT2*C related genotypes and alleles are associated with asthma susceptibilities and pathogenesis. There were non-association and non-additional effects of TLR4/CD40 gene polymorphisms and haplotypes upon asthma risk.
哮喘由多种基因与环境因素之间的复杂相互作用引起。在此，我们旨在研究信号转导和转录激活因子2（STAT2）、Toll样受体4（TLR4）及CD40相关多态性是否与哮喘易感性相关。
将儿童分为：（1）哮喘组（n = 117）；（2）正常对照组（n = 60）。采用聚合酶链反应-限制性片段长度多态性基因分型法分析STAT2、TLR4和CD40的多态性。比较两组的基因型、等位基因频率及单倍型关联。
与哮喘易感性较高相关的是STAT2C相关基因型，而非TLR4和CD40多态性。两组中STAT2CC/CG/GG和C/G等位基因的分布分别为：（1）0/11.1/88.9%和5.6/94.4%；（2）0/1.7/98.3%和0.8/99.2%（p<0.05）。TLR4rs10983755 AA/AG/GG和rs1927914 CC/CT/TT纯合子的比例分别为：（1）35.1/8.5/56.4%和9.4/56.4/34.2%；（2）35/8.3/56.7%和16.7/48.3/35%（无差异）。CD40rs1883832 CC/CT/TT、rs3765459 AA/AG/GG和rs4810485 TT/GT/GG的比例分别为：（1）29.9/53/17.1%，6.8/47.9/45.3和18.8/62.4/18.8%；（2）36.7/41.7/21.6%，1.6/46.7/51.7和15/51.7/33.3%（无差异）。TLR4和CD40基因的单倍型分析显示它们与哮喘易感性无关联且无附加效应。
STAT2*C相关基因型和等位基因与哮喘易感性及发病机制相关。TLR4/CD40基因多态性和单倍型与哮喘风险无关联且无附加效应。
