STAT6 polymorphisms are associated with neonatal regulatory T cells and cytokines and atopic diseases at 3 years. Issue 10 (21st September 2013)

• Record Type: Journal Article
• Authors: Casaca, V. I.; Illi, S.; Klucker, E.; Ballenberger, N.; Schedel, M.; von, E.; Kabesch, M.; Schaub, B.
• Is Part Of: Allergy. Volume 68:Issue 10(2013:Oct.)
• Page Start: 1249
• Page End: 1258
• Publication Date: 2013-09-21
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12220
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12220-abs-0001"> <title>Abstract</title> <sec id="all12220-sec-0001" sec-type="section"> <title>Background</title> <p>The transcription factor STAT6 is crucial for activation of the interleukin (IL)‐4/IL‐13 pathway and has been linked to regulatory T cells (Tregs). Associations of <italic>STAT6</italic> polymorphisms with IgE levels were described; however, their impact on neonatal immune responses and early disease development is unknown.</p> </sec> <sec id="all12220-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>STAT6</italic> polymorphisms were genotyped in cord blood mononuclear cells by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). Gene expression was assessed by real‐time polymerase chain reaction (PCR) and cytokines by Multiplex. At age 3 years, atopic diseases were assessed by questionnaires.</p> </sec> <sec id="all12220-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>STAT6</italic> rs324011 but not rs1059513 polymorphism was associated with significant or borderline significant decreased mRNA expression of Treg‐associated genes (<italic>FOXP3</italic>, <italic> GITR</italic>, <italic> LAG3)</italic>. Heterozygotes and minor allele homozygotes of rs324011 had low levels of tumor necrosis factor alpha (TNF‐α) and increased interferon gamma (IFN‐γ) (<italic>P </italic>≤ 0.04), while heterozygotes and minor allele homozygotes of rs1059513 had increased TNF‐α and Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) (<italic>P</italic> ≤ 0.05). In minor allele homozygotes of rs324011, expression of Treg‐associated genes was strongly inverse correlated with IFN‐γ (unstimulated, <italic>r</italic> = −0.7, <italic>P</italic> = 0.111; LpA stimulation, <italic>r</italic> = −0.8, <italic>P</italic> = 0.011), but not in heterozygotes or major allele homozygotes. Heterozygotes and minor allele homozygotes of rs324011 presented a lower risk of atopic dermatitis and obstructive bronchitis until age 3 years.</p> </sec> <sec id="all12220-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Two <italic>STAT6</italic> polymorphisms were associated with altered immune responses already at birth. <italic>STAT6</italic> rs324011 was associated with lower neonatal Treg and increased Th1 response. Those neonates had a lower risk of atopic dermatitis and obstructive bronchitis until 3 years. Our data suggest a role for <italic>STAT6</italic> polymorphisms in early immune regulation and implications on early atopic disease development.</p> </sec> </abstract>