A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels

Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background

“…Frequencies of genotyped SNPs were similar to SNP frequencies reported in similar studies (In2-SNP3, In18 and 3UTR SNP4 polymorphism investigated in this study as well as in German studies), differences in allelic frequencies were up to 5% (ref. 9,45 ) and the allelic frequencies were also similar compared to the population of asthmatics in a study of 1500 subjects by Schedel et al 12 . Haplotype analysis revealed that the most common STAT6 haplotype -s1 haplotype (ATTCAA) -is significantly associated with the elevation of total IgE levels.…”

“…Hence none of the SNPs reached significant level (Table 2), some of the SNPs (such as In2 -SNP3) were more often present in patients with asthma or with increased total IgE levels. This result was not surprising because some of these SNPs (such as In2-SNP3, In17, In18, 3UTR-SNP4) were associated with elevated total IgE levels, or with decline in lung function (FEV 1 ) in some studies 11,12,43 but not in others 12,44 . This difference could be explained by different patient group size in the studies, however, international studies working with hundreds/thousands of asthma patients of Caucasian origin didn't find statistically significant differences in the distribution of investigated polymorphisms between the group of asthmatics and the control group 43,44 .…”

“…The C2892T (rs324011) polymorphism in the second intron of STAT6 has been repeatedly associated with elevated IgE in the German population 11 . The T12888C (rs1059513) and A4671G (rs4559) have also showed a significant link with elevated IgE level in the German population 11,12 . Nagarkatti et al 33 identified and associated the CA repeating polymorphism (R1 locus) in the promoter region of STAT6 with atopic asthma in the Indian population.…”

“…Many studies have shown linkage of the chromosomal locus 12q13-24 to asthma or associated phenotypes, such as elevated IgE level [8][9][10] . A signal transducer and activator of transcription 6 (STAT6), as one of the asthma candidate genes, was found in this region and some of the association studies focused on the STAT6 SNPs have shown their linkage to IgE levels 11,12 . Human STAT6 is located on 12q13.3-14.1 and contains 23 exons 13 ( Fig.…”

“…Another study conducted on the German population found haplotype CGTGTT to be associated with elevated IgE (ref. 12 ). Environmental influences and epigenetic mechanisms could pose important modifying factors shaping the phenotype at a clinical level.…”