Witte John S, Palmer Lyle J, O'Connor Richard D, Hopkins Penelope J, Hall Jeff M
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106-4945, USA.
Eur J Hum Genet. 2002 Jan;10(1):82-5. doi: 10.1038/sj.ejhg.5200746.
Tumour necrosis factor (TNF) alpha affects immune response and airway inflammation, which are characteristics of asthma. Genetic factors may impact TNFalpha levels, and several polymorphisms in the TNF gene cluster on chromosome 6p21 have been associated with TNFalpha production and potential increased risk of asthma. The present paper evaluates the relation between two single nucleotide polymorphisms (SNPs) in the TNF gene cluster and asthma risk. The SNPs investigated here are guanine (G) to adenosine (A) substitutions in the TNFalpha and lymphotoxin alpha (LTalpha) genes. The TNFalpha SNP is at position -308 in the promoter region (TNFalpha-308), while the LTalpha SNP is in the first intron NcoI recognition sequence (LTalpha-NcoI). (For both SNPs the G allele is denoted as 1, and the A allele 2.) We determined TNFalpha-308 and LTalpha-NcoI genotypes in 511 individuals: 236 asthma cases and 275 non-asthmatic controls. Data were analysed by logistic regression of asthma status on the genotypes and potential confounders. TNFalpha-3082 was positively associated with asthma, and this relation was strengthened when restricting cases to individuals reporting acute asthma: the adjusted odds ratio (OR) comparing carriers of one or two TNFalpha-3082 alleles versus none was 1.86 (95% confidence interval (CI)=1.03-3.34, P=0.04). Further restricting the subjects to those with a family history of asthma, and those of European-American ancestry strengthened the association even more: adjusted OR=3.16 (95% CI=1.04-9.66; P=0.04). LTalpha-NcoI1 was weakly associated with asthma, and analysis of both genes suggests that only the TNFalpha-3082 allele increases risk of asthma.
肿瘤坏死因子（TNF）α影响免疫反应和气道炎症，而这两者都是哮喘的特征。遗传因素可能会影响TNFα水平，并且位于6号染色体p21上的TNF基因簇中的几种多态性与TNFα的产生以及哮喘潜在的患病风险增加有关。本文评估了TNF基因簇中的两个单核苷酸多态性（SNP）与哮喘风险之间的关系。此处研究的SNP是TNFα和淋巴毒素α（LTα）基因中鸟嘌呤（G）到腺嘌呤（A）的替换。TNFα SNP位于启动子区域的 -308位（TNFα -308），而LTα SNP位于第一个内含子NcoI识别序列中（LTα -NcoI）。（对于这两个SNP，G等位基因记为1，A等位基因记为2。）我们确定了511名个体的TNFα -308和LTα -NcoI基因型：236例哮喘患者和275名非哮喘对照者。通过对哮喘状态与基因型及潜在混杂因素进行逻辑回归分析数据。TNFα -3082与哮喘呈正相关，当将病例限制为报告有急性哮喘的个体时，这种关系得到加强：比较携带一个或两个TNFα -3082等位基因的个体与不携带该等位基因的个体，调整后的比值比（OR）为1.86（95%置信区间（CI）=1.03 - 3.34，P = 0.04）。进一步将受试者限制为有哮喘家族史且为欧美血统的个体，这种关联更强：调整后的OR = 3.16（95% CI = 1.04 - 9.66；P = 0.04）。LTα -NcoI1与哮喘呈弱相关，对两个基因的分析表明只有TNFα -3082等位基因会增加哮喘风险。
