Association between polymorphism of tumour necrosis factor  -308 gene promoter and asthma: a meta-analysis

Abstract

Background: Asthma is a complex polygenic disease in which gene-environment interactions are important. The gene encoding tumour necrosis factor alpha (TNFa) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNFa-308 gene promoter (substitution GRA, designated as TNF1 and TNF2) in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Methods: To address the inconsistent findings in studies of the association of the polymorphism of TNFa-308 gene promoter with susceptibility to asthma, a systematic review was undertaken of the published data and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to October 2005. Data were extracted using standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Fifteen eligible studies, comprising 2409 patients with asthma and 3266 controls, were included in the meta-analysis. Using the random effects model, the pooled result showed that the TNF2 allele is associated with overall susceptibility to asthma (OR 1.37, 95% CI 1.02 to 1.84, p = 0.04). The ORs for asthma susceptibility in TNF2 homozygote individuals were significantly increased at 2.01 (95% CI 1.26 to 3.20, p = 0.009) and 1.51 (95% CI 1.02 to 2.22, p = 0.041) compared with TNF1 homozygotes and TNF2/1 heterozygotes, respectively. In addition, the pooled OR for asthma risk in TNF2/1 heterozygotes was also significantly higher than that in TNF1/1 homozygotes (OR 1.47, 95% CI 1.01 to 2.13, p = 0.045). Conclusions: The TNF2 allele confers a significant risk for developing asthma. A large scale case-control study is needed to clarify the functional effect of the polymorphism of the TNFa gene in the pathogenesis of asthma.

Polymorphisms of <i>PHF11</i> and <i>DPP10 </i> Are Associated with Asthma and Related Traits in a Chinese Population

“…Statistically, there is increased power in studying the equivalent number of individuals in case-control association studies than in family-based studies [18]. However, small population sizes, population stratification, phenotype heterogeneity and varied environmental exposure are often blamed for negative replication of initially positive associations [10,29]. The current study has some advantages.…”

“…Genetic risk factors for asthma have often differed among different populations [10]. This may be caused by phenotypic heterogeneity, different ethnicity and linkage disequilibrium (LD) patterns.…”

Genetic Predisposition to Asthma and Atopy

“…We identified 10 meta-analyses of specific gene variants for asthma [1,2,3,4,5,6,7,8,9,10]. They evaluated single nucleotide polymorphisms (SNPs) for 5 genes [tumor necrosis factor alpha ( TNFA , n = 2 meta-analyses), β 2 -adrenergic receptor ( B2AR , n = 4 meta-analyses), a disintegrin and metalloprotease 33 ( ADAM33 , n = 2 meta-analyses), CD14 , and leukotriene C4 synthase (LTC4S) ].…”

Tumor Necrosis Factor-α −308G&gt;A Allelic Variant Modulates Iron Accumulation in Patients with Hereditary Hemochromatosis

“…A possible role of the TNF-␣ Ϫ308GϾA allelic variant has been investigated in several diseases. The TNF-␣ Ϫ308A allele was positively associated with manifestations of inflammatory processes such as septic shock (16 ), cerebral malaria (17 ), Crohn disease (18 ), and asthma (19 ); however, not all studies confirmed these associations (20 -23 ). No significant association or controversial results have been reported in studies investigating the role of the TNF-␣ Ϫ308AϾG allelic variant in coronary artery disease (24 -26 ), type 2 diabetes (27 ), or hypertension (28,29 ).…”