Polymorphisms of the IL-4, TNF- α , and Fc α RI β Genes and the Risk of Allergic Disorders in At-risk Infants

Abstract

Polymorphisms in the TNF-alpha (A-308G), IL-4 (C-589T), and Fcalpha RIbeta (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. Phenotypic data were collected for atopy and allergic diseases in the infants at 12 mo of age. The prevalence of these phenotypes in the 281 white infants was compared in each genotypic group. There were no differences in the prevalence of any phenotype between genotypes of the TNF-alpha and Fcalpha RIbeta polymorphisms. However, we found that the IL4-589*T allele was associated with "probable" asthma (RR = 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR = 2.4). Using the transmission disequilibrium test, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-alpha-308*2 or Fcalpha RIbeta*G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.

A complete screening of the IL4 gene

“…These findings are in accordance with previously published results, in which C-589T linked the polymorphism in T-589 to increased total serum IgE levels in a group of 44 asthmatic patients 6 and fatal/near-fatal asthma, as well as "probable" asthma. 23,24 In contrast, a large study conducted in 1128 children from Australia and England could not find associations between the C-589T polymorphism and atopic phenotypes, 25 except for a weak association with specific IgE against house dust mites in Australian, but not in English, children. Japanese studies reported linkage between the IL4 promoter polymorphism and atopic dermatitis 9 and asthma 8 in 68 Japanese families.…”

An association between asthma and TNF-308G/A polymorphism: meta-analysis

“…1; Moffatt and Cookson 1997;Albuquerque et al 1998;Louis et al 2000;Winchester et al 2000;Buckova et al 2002;Witte et al 2002;El Bahlawan et al 2003;Sandford et al 2004;Shin et al 2004;Wang et al 2004;Bilolikar et al 2005;Gupta et al 2005). Several studies were not included because allele frequency data were not available (Chagani et al 1999;Li Kam Wa et al 1999;Trabetti et al 1999;Lin et al 2002;Di Somma et al 2003;Li et al 2006) or because of an incomplete phenotype (probable asthma; Zhu et al 2000). We also excluded the family-based association study (Randolph et al 2005) and a study of occupational asthma (Beghe et al 2004) from our meta-analysis.…”

“…Some studies have supported an association with asthma (Moffatt and Cookson 1997;Albuquerque et al 1998;Chagani et al 1999;Li Kam Wa et al 1999;Winchester et al 2000;Witte et al 2002;Shin et al 2004;Wang et al 2004), whereas other studies have not (Louis et al 2000;Zhu et al 2000;Buckova et al 2002). Moffatt and Cookson (1997) first reported that -308G/A was significantly associated with asthma in an Australian population (Moffatt and Cookson 1997).…”

The pharmacogenetics of asthma: a candidate gene approach

“…[53][54][55][56] Although genetic loci directly related to GC-resistant asthma have yet to been determined, sequence variants associated with asthma, asthma severity and atopy have been detected in the IL-4 promoter (Ϫ590, C to T), TNF-␣ promoter (Ϫ308, A to G), and Fc⑀RI␤ (576, Ala to Arg) in some but not all studies. [57][58][59] …”