Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthma-related phenotypes.
Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthma-related phenotypes.
复制标题
肿瘤坏死因子基因簇中的扩展单倍型与哮喘和哮喘相关表型相关。
DOI：
10.1164/rccm.200501-122oc
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发表时间：
2005
影响因子：
24.7
通讯作者：
Weiss,ScottT
中科院分区：
文献类型：
--
作者：
Randolph,AdrienneG;Lange,Christoph;Silverman,EdwinK;Lazarus,Ross;Weiss,ScottT
肿瘤坏死因子是一种促炎细胞因子，在哮喘气道中浓度增加。TNF-α（TNF）和α-光毒素-α（LTA）基因属于TNF基因超家族，位于人类主要组织相容性复合体染色体6p上与哮喘重复相关的区域。TNF-308和LTANcoI多态性被认为分别影响TNF转录和分泌，ObjectiveThis study seemed to determine whether polymorphisms in TNF or LTA，or in TNF-LTA haplotypes，are associated with asthma and asthma phenotypes.MethodsWe genotyped TNF-308和LTANcoI多态性，以及TNF和LTA基因中另外两个单倍型标记多态性，708名轻度至中度哮喘儿童参加了儿童哮喘管理项目及其父母。在PBAT项目中使用扩展的基于家族的关联性检验，检验每个多态性与哮喘、哮喘发作时的年龄、基线FEV1%预测值、支气管扩张剂后FEV1%预测值、体重指数和PC 20对数的时间序列数据的关联性。测量和主要结果尽管未发现单个单核苷酸多态性与哮喘的关联性，单倍型分析发现LTANcoI_G/LTA 4371 T/TNF-308 G/TNF-1078 G单倍型与哮喘及所有5个表型组相关。但是这种变体的单倍型可能是功能性的，或者可能与其它功能性单核苷酸多态性连锁不平衡。
RationaleTumor necrosis factor is a proinflammatory cytokine found in increased concentrations in asthmatic airways. The TNF-α (TNF) and lymphotoxin-α (LTA) genes belong to the TNF gene superfamily located within the human major histocompatibility complex on chromosome 6p in a region repeatedly linked to asthma. The TNF position –308 and LTANcoI polymorphisms are believed to influence TNF transcription and secretion, respectively.ObjectivesThis study sought to determine whether polymorphisms in TNF or LTA, or in TNF-LTA haplotypes, are associated with asthma and asthma phenotypes.MethodsWe genotyped the TNF –308 and LTANcoI polymorphisms, and two other haplotype-tagging polymorphisms in the TNF and LTA genes, in 708 children with mild to moderate asthma enrolled in the Childhood Asthma Management Program and in their parents. Using an extension of the family-based association tests in the PBAT program, each polymorphism was tested for association with asthma, age at onset of asthma, and time series data on baseline FEV1% predicted, postbronchodilator FEV1% predicted, body mass index, and log of PC20.Measurements and Main ResultsAlthough no associations were found for the individual single-nucleotide polymorphisms, the haplotype analysis found the LTANcoI_G/LTA 4371T/TNF –308G/TNF 1078G haplotype to be associated with asthma and with all five phenotype groups.ConclusionsWe conclude that it is unlikely that the TNF –308 or LTANcoI polymorphisms influence asthma susceptibility individually, but that this haplotype of variants may be functional or may be in linkage disequilibrium with other functional single-nucleotide polymorphisms.