Linkage and association of childhood asthma with the chromosome 12 genes

Abstract

Several studies have shown linkage of chromosome region 12q13-24 to bronchial asthma and related phenotypes in ethnically diverse populations. In the Japanese population, a genome-wide study failed to show strong evidence of linkage of this region. Chromosome 12 genes that showed association with the disease in at least one report include: the signal transducer and activator of transcription 6 gene (STAT6), the nitrogen oxide synthetase 1 gene (NOS1), the interferon c gene (IFNG), and the activation-induced cytidine deaminase gene (AICDA). To evaluate the linkage between chromosome 12 and childhood asthma in the Japanese population, we performed sib-pair linkage analysis on childhood asthma families using 18 microsatellite markers on chromosome 12. To investigate association between chromosome 12 candidate genes and asthma, distributions of alleles and genotypes of repeat polymorphisms of STAT6, NOS1, and IFNG were compared between controls and patients. Single nucleotide polymorphism of AICDA was also investigated. Chromosome region 12q24.23-q24.33 showed suggestive linkage to asthma. The NOS1 intron 2 GT repeat and STAT6 exon 1 GT repeat were associated with asthma. Neither the IFNG intron 1 CA repeat nor 465C/T of AICDA showed any association with asthma. Our results suggest that NOS1 and STAT6 are asthmasusceptibility genes and that chromosome region 12q24.23-q24.33 contains other susceptibility gene(s).

A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study

“…IL-13, in conjunction with IL-4, is a critical mediator of the T H 2 allergic response and STAT6 is considered the master regulator of IgE class switch recombination. 32-33 Our observation of a strong association of STAT6 SNPs with IgE concentration confirms previous linkage and candidate gene studies which have shown STAT6 genetic variants to be associated with food allergy, 34 atopic dermatitis, 35 asthma, 36 and total IgE. 37 In a recent review of asthma and atopy genetics, Ober and Hoffman identified IL-13 as one of 8 “elite” genes which had been associated with an asthma or atopy phenotype in greater than 10 studies.…”

The Correlation Analysis of Two Common Polymorphisms in STAT6 Gene and the Risk of Asthma: A Meta-Analysis

“…Shao et al . [13] also found a significant difference in allelic distributions between patients and control subjects, but the frequency of GT 15 allele is the only difference detected. Other studies have also reported negative results [14] or even opposite conclusions [30].…”

“…Among these case-control studies, five studies described GT dinucleotide repeat length polymorphism [11]–[15] and seven studies investigated G2964A polymorphism [5]–[10]. Among the studies on GT repeat length polymorphism, four studies involved Asian populations, in which two focused on Chinese populations [14], [15] and the remaining two considered Japanese populations [12], [13]. One study focused on a Caucasian population specifically the British population [11].…”

“…Children/adults or both populations were included in the studies. However, three studies did not provide a detailed age group of the population investigated [5], [11], [13]. Polymerase chain reaction-based genotyping methods were provided in all of the studies ( Table 1 ).…”

Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

“…Synergy between IL-4 and CD40 might be required to achieve a threshold level of AICDA expression for CSR to IgE [13]. Several groups have reported an association between serum IgE levels, allergic disorders, and polymorphisms in the AICDA gene [14–16], although this association is not completely understood and might vary among populations [17, 18]. …”