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Background Food allergy (FA) may be IgE-mediated, non-IgE-mediated or mixed. Genetic predispositions result in dysregulation of the immune system and lead to FA when exposed to environmental triggers. The transcription factor STAT6 is activated by IL-4 and IL-13 and activates cytokine signaling in immune and target tissue cells; contributing in the pathogenesis of allergic disorders including FA. The rs324015 single nucleotide polymorphism (SNP) in the STAT6 gene was previously associated with nut and cow’s milk allergy. Objective to investigate the association of the rs324015 STAT6 gene SNP with food allergy. Patients and Methods After ethical committee approval and informed consent from the patients, this retrospective case control study was conducted on 100 Egyptian children divided into two groups. Group I consisted of 50 children with positive history of FA supported by positive skin prick test +/- oral food challenge and group II consisted of 50 healthy age-matched controls. Blood samples were collected and genotyped using Taqman® Realtime PCR assays. Results We found that the homozygous G genotype and G allele of rs324015 were significantly higher among food allergic subjects than controls. We report no effect of any specific genotype on the phenotype of allergic disease or reacting to a specific food more than others. Genotypes were also not related to disease severity, eosinophil counts, total IgE levels or a family history of atopic disease. Conclusion rs324015 STAT6 gene SNP may be involved in the pathophysiology of food allergy.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER). Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2-STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (sig-nal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2-STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neo-plasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8-STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.

Fifty-five cases of t(14;18)− follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)− FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)− FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)+ FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)− FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P < .05). STAT6 mutations showed a positive correlation with CD23 expression (P < .001). In summary, t(14;18)− FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.

Multiple sclerosis (MS) is a complex inflammatory, autoimmune disease of the central nervous system (CNS). The disease pathogenesis is not well defined yet. Cytokines have an important role in inflammation as characteristic feature of the disease. Janus kinase/signal transducers and activators of transcriptions (JAK/STAT) family promote cytokine-mediated cell activation. Failure in the JAK/STAT signaling pathway is associated with the pathological outcome in MS. In this study, we compared the expression levels of STAT5a and STAT6 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We found that STAT5a expression was significantly down-regulated (p = .049), whereas STAT6 gene expression was significantly up-regulated (p = .046) in MS patients compared with controls. Moreover, there was significant correlation between the STAT6 gene expression and Kurtzke Expanded Disability Status Scale (EDSS) criterion. However, no significant correlation was demonstrated between the expression of STAT5a gene and clinical findings. Furthermore, there was not significant correlation between expression levels of STAT5a and STAT6 genes. Our findings suggest that STAT5a and STAT6 dysregulation may have a critical role in modification of immune responses leading to imbalance between Th2- and Th1-related cytokines. However, the mechanisms underlying it still remain to be elucidated. Future studies are needed to explore the role of STAT5a and STAT6 as prognostic biomarkers in research, design of experimental therapies or clinical settings of the MS.

The aim of this research was to analyze the distribution of FTO and STAT6 genes polymorphism in patients with bronchial asthma (BA), associated with obesity (Ob) depending on the main disease severity degree. Materials and methods. The study included 117 patients 18–48 years old, divided in 3 groups. The main group (bronchial asthma, associated with obesity) included 57 patients, two groups of comparison – 30 patients with the diagnosis BA and a normal body weight, and 30 patients with obesity, but without the pathology of the bronchopulmonary system. The general genomic DNA was extracted from blood according to the standard protocol. The genetic typing was realized by the method of allele-specific amplification with the detection of results in the real time regime using TaqMan-probes, complementary to polymorphic parts of DNA. The detection of deletions in FTO and STAT 6 genes was realized by the method of polymerase chain reaction (PCR) using specific primers. Results. In the main group, among patients with BA and Ob, carriers of Т/Т genotype were 36,84 %, Т/А – 45,61 %, А/А – 17,55 % against 40 %, 60 % and 0 % respectively in PHP group by FTO gene. Carriers of С/С genotype in the main group were 38,6 %, С/Т – 35,09 %, Т/Т – 26,31 % against 40 %, 55 % and 5 % respectively in PHP group by STAT6 gene. In the main group the light persisting BA was diagnosed in 20,0 % of cases, middle severity – in 60,0 % and severe – in 20,0 % of patients. In the group of comparison this disease severity was observed in 17,7 %, 66,5 % and 15,8 % of observations, respectively. Conclusions. So, among patients with BA, associated with Ob with the middle and severe course of asthma the percent of heterozygous (Т/А) and mutant carriers (А/А) rs9939609 polymorphism of FTO gene is higher than at the light course. The analogous situation is observed at the study of rs324011 polymorphism of STAT6 (C2892T) gene among this category of patients. So, the determination of FTO and STAT6 genes polymorphism in patients with BA, associated with Ob, can be considered as a marker of the more severe course of asthma.

Background Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes (STAT5 and STAT6) on the biological activities of CRC cells via the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. Methods We initially screened the GEO database for differentially expressed lncRNAs related to CRC and then made a prediction of the implicated target genes. Then we collected CRC tissues and adjacent normal tissues from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with small interference RNA (siRNA) against RP11-468E2.5, AG490 (an inhibitor of the JAK/STAT signaling pathway), or both in combination. Next, we measured the effects of RP11-468E2.5 treatment on cellular activities such as cell viability, cycle distribution and cell apoptosis, and studied interactions among RP11-468E2.5, STAT5/STAT6, and the JAK/STAT signaling pathway. Finally, an in vivo tumor formation assay was performed to observe the effect of RP11-468E2.5 on tumor growth. Results The CRC-related gene microarray data showed low expression of RP11-468E2.5 in CRC surgical specimens. However, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participate in the JAK/STAT signaling pathway. CRC tissues showed lower expression of RP11-468E2.5, higher expression of STAT5, STAT6 and of the cell cycle marker Cyclin D1 (CCND1), compared to the findings in adjacent normal tissues. The treatment of siRNA against RP11-468E2.5 increased expression of JAK2, STAT3, STAT5, STAT6, CCND1 and Bcl-2 along with the extent of STAT3, STAT5 and STAT6 phosphorylation, while lowering expression of P21 and P27. Treatment with AG490 exhibited approximately opposite effects, whereas siRNA against RP11-468E2.5 treatment stimulated CRC cell proliferation and reduced cell apoptosis, while promoting cell cycle entry; AG490 treatment reversed these results. Conclusions Altogether, we conclude that up-regulation of RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.

This work was performed to evaluate the level of IL-4, and to clarify the role of IL-4 gene polymorphism at position cytosine -590-to-thyamine (C-590T), IL-4Rα gene polymorphism at position adenine +4679-to-guanine (A+4679G) [isoleucine-50-valine (I50V)] and STAT6 gene polymorphism at position guanine 2964-to-adenine (G2964A) in Saudi children with non-atopic dermatitis (non-AD) and atopic dermatitis (AD) to identify their role in the pathogenesis of these diseases.This study included 150 children: 50 healthy children as controls, 50 with non-AD, and 50 with AD. They were subjected to full clinical examination, complete blood picture, skin prick test, and determination of serum interleukin-4 (IL-4) and total immunoglobulin-E (IgE) levels. Detection of interleukin-4 gene (C-590T), interleukin-4 receptor alpha gene (A+4679G) (I50V), and STAT6 gene (G2964A) polymorphisms were performed by PCR-based restriction fragment length polymorphism (PCR-RFLP).There was a significant (P0.01) association between genotype and allele frequencies of IL-4Rα (A+4679G) (I50V) polymorphism in the AD group (but not non-AD group). Moreover, there was a significant association between genotype and allele frequencies of the STAT6 (G2946A) polymorphism in the non-AD (P0.05) and AD (P0.01) groups. On the other hand, there was no significant association between genotype and allele frequencies of the (C-590T) polymorphism in the non-AD group and AD group. There was a significant (P0.001) higher total IgE level in patients compared to the controls. Moreover, the mean values of total IgE were significantly different among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively, in all the studied groups. On the other hand, there was no significant difference of serum IL-4 levels among all the studied patients, or among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively.IL-4Rα gene (I50V) and STAT6 gene (G2964) polymorphisms may play a role in development of eczema; however, the IL-4 gene polymorphism (C-590T) had no relationship with susceptibility to the disease among Saudi children.

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analyzed including 262 children (71.0%) with food allergy. Associations were tested by family based association testing (FBAT). The A alleles of both SNPs were associated with food allergy (p=0.036 and p=0.013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all p

IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Ige via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Ige promoter regions. Our results revealed that the Ige gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.

T helper 2 (Th2) cytokines are known to be important in protection against experimental autoimmune encephalomyelitis (EAE). To investigate the role of the signal transducer and activator of transcription factor 6 (STAT6) in EAE we used mice with two different targeted disruptions of the STAT6 gene. In this report, we show that mice with a targeted deletion of the first coding exon of the SH2 domain of STAT6 induce Th2 cell differentiation and are resistant to EAE induction. By contrast, STAT6 −/− mice generated by deletion of amino acids 505 to 584 encoding the SH2 domain of STAT6 are defective in Th2 cell differentiation and develop very severe EAE. These results suggest that an altered STAT6 gene can be more efficient than wild type STAT6 in regulating the autoimmune response in EAE.

BACKGROUND: The aim of the study was to test whether the signal transducer and activator of transcription 6 (STAT6) gene influences the risk of developing endometriosis. METHODS: The single-nucleotide polymorphism, G2964A, in the 3'-untranslated region (UTR) of the STAT6 gene was tested for association in a case-control study of 232 affected women and 210 women with no evidence of disease. All the women were infertile, ascertained from the same infertility clinic and of South Indian origin. The genotype frequencies of this polymorphism were compared using PCR and sequencing analysis. RESULTS: There were statistically significant differences in the genotype distributions (P = 0.002) and allele frequencies (P = 0.0002) between the cases and controls, according to codominant, dominant and recessive genotype models. CONCLUSIONS: We report for the first time an association between the STAT6 G2964A 3'-UTR polymorphism and endometriosis in South Indian women. This finding suggests that STAT6 may contribute to disease susceptibility in endometriosis, which carries an extra interest as the gene lies in a region which has been implicated, albeit weakly, in a previous genomewide scan.

Background/Aims: Minimal change nephrotic syndrome (MCNS) in children is frequently associated with allergy and immunoglobulin E (IgE) production. T-helper subtype 2 cytokines, such as interleukin (IL)-4 and IL-13, have been implicated in the regulation of IgE production. We investigated the associations of gene polymorphisms of IL-4, IL-13, and signal transducer and activator 6 (STAT6) in Indonesian children with MCNS (n = 84) and controls with neither allergic nor renal disease (n = 61). Methods: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the IL-4 promoter gene polymorphism (–590C/T) and IL-13 gene polymorphism (4257G/A), and direct sequencing was used for the STAT6 3S untranslated region (2964G/A) polymorphism. Results: There was a significant difference between the MCNS group and the controls in the genotypic distribution of IL-4 and IL-13 gene polymorphism. In the case of the IL-4 promoter gene, the frequency of the CC homozygote was significantly lower in the MCNS group than in the controls, while, in the case of IL-13, the frequency of the GG homozygote was significantly lower in the MCNS group. However, there was no difference between the MCNS group and the controls in the STAT6 gene polymorphism. Conclusion: The genetic variations in the IL-4 and IL-13 genes may be associated with predisposition to MCNS.

Background: Signal transducer and activator of transcription 6 (STAT6) is a key transcription factor involved in both interleukin-4 (IL-4) and IL-13-mediated biological responses, such as allergies. Recently, we reported that the polymorphism of the STAT6 gene exon 1 was associated with allergic diseases, while another group studied the G2964A variant of the STAT6 gene’s association with atopic asthma. We undertook an association study between these variants of the STAT6 gene and allergic diseases, including atopic dermatitis, bronchial asthma, and food-related anaphylaxis in a Japanese population. Methods: STAT6 gene polymorphisms were genotyped by polymerase chain reaction (PCR) fragment length polymorphism analysis, and PCR-SSCP analysis in 106 allergic and 66 control subjects. Results: The 2964A variant was in significant linkage disequilibrium with the dinucleotide repeat polymorphism, the 13-GT repeat allele of STAT6 exon 1 (p < 0.0000000003). There was no association between the STAT6 2964A variant and allergic subjects in a Japanese population (p = 0.2724). The genotype of 13/15-GT repeat allele heterozygosity was significantly associated with allergic subjects (p = 0.0006), as previously reported. In one major genotype of the STAT6 exon 1 (15 GT repeat homozygosity), wild-type 2964G allele homozygosity was significantly associated with allergic subjects (p = 0.0382). Conclusions: Our findings indicate that in combination the dinucleotide repeat polymorphism of the STAT6 exon 1 gene and the 2964A variant may be useful markers for predicting allergic diseases in a Japanese population.

The current study will investigate the mechanosensory-signaling pathway leading to STAT6 gene transcription in mouse cortical collecting duct epithelial cells. Many stimulants are capable of activating STAT6 in the kidney, but it is still unknown how STAT6 is directed to specific gene targets. In several cases, transcription co-factors, such as a fragment of polycystin 1, have been found to enter the nucleus along with STAT6 dimers. Additionally, the mechanism by which STAT6 becomes activated by mechanosensation is currently unknown. A primary goal of this study is to determine the kinase involved in STAT6 phosphorylation (activation) in changing flow conditions. The STAT family has cell-type specific promoter binding sites. Common STAT controlled cis-regulatory modules (cSCCs) are cis-regulatory modules (CRMs) that can be recognized by all STAT family members across cell types. 116 cSCCs have been identified and correspond to JAK/STAT signaling genes. I hypothesize that different stimulants (cytokines vs...

Background and aims. Linkage of inflammatory bowel diseases to chromosome 12p13.2–q24.1 (IBD2) has been confirmed in several genome wide screens. The STAT6 gene is located within this chromosomal region. The transcription factor STAT6 is involved in the regulation of the TH1/TH2 immune response. Increased production of TH1 cytokines is crucial in the pathogenesis of Crohn's disease. Patients and methods. Therefore, we genotyped a single nucleotide polymorphism in the 3′ untranslated region of the STAT6 gene (G2964A) in 243 patients with Crohn's disease, 100 patients with ulcerative colitis and 548 healthy controls. Results. In comparison to controls, the G allele and the GG genotype frequencies were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene (p Conclusions. Alterations in the STAT6 pathway may play a crucial role in the pathogenesis of distinct subgroups of patients with Crohn's disease.

Parasites remain competent invaders of host immunity. Their invasion strategies have proven to impact immunorelevant genes leading to diversity among gene families. We focussed on signal transducer and activator of transcription (STAT6) factor that plays a fundamental role in signal transduction and activation of transcription. Recent studies have highlighted the role of STAT6 variants in control of infection levels. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the STAT6 gene in a group of Gabonese individuals exposed to a variety of parasitic infections. Three promoter variants were identified in 40 individual subjects. We further validated these promoter variants for their allelic gene expression using transient transfection assays. One promoter variant, rs3024944 (G/C), revealed an altered expression of the marker gene. The identification of function-altering SNPs in the promoter may facilitate studying parasite susceptibility in association studies.

Three hundred million individuals are at risk of infection by schistosomes, which cause severe kidney and liver disease, and 280 000 deaths annually. Infection levels are mainly under the control of a major locus, SM1 (Schistosoma mansoni 1), mapped in 5q31q33 region. An association between the rs1800925 polymorphism in the IL13 promoter and infection levels was detected. Subjects bearing the rs1800925T/T genotype were much less infected than individuals with other genotypes. We went on to investigate whether other polymorphisms in genes involved in the TH2 cytokine immune response could affect susceptibility to schistosome infection. An association between STAT6 rs324013 polymorphism and infection levels was also found. These two polymorphisms which have an additive effect were not strongly correlated with any other tested markers surrounding the two genes. Moreover, these polymorphisms affect transcription factor binding to the promoter regions. These results are consistent with the TH2 cytokine pathway enhancing resistance to schistosome infection. Key concepts: IL13 gene is associated to the control of infection levels in schistosomiasis. STAT6 gene is associated to the control of infection levels in schistosomiasis. IL13 and STAT6 polymorphisms have synergic effect. Keywords: schistosomiasis; infection; IL13; STAT6; gene; parasitic

STAT6 transcription factor, which has been implicated in commitment to Th2, is known to be activated by IL-4 and IL-13. Accordingly, STAT6 is primarily responsible for the transcriptional effects of IL-4 and IL-13. STAT6-deficient mice are known to have defective IL-4-mediated functions, such as B cell proliferation, Th2 cell development and IgE secretion; therefore, they primarily contain the Th1 phenotype. However, the mechanism responsible for regulation of STAT6 expression transcriptionally and post-transcriptionally has yet to be elucidated. Here, we characterized the human STAT6 promoter gene and found that the transcriptional regulatory elements CCAAT and ATF were important for the STAT6 promoter activity. Direct sequencing analysis revealed that the 13 GT repeat allelic variation in noncoding exon 1 of the STAT6 gene appeared more frequently in 91 patients with asthma or rheumatoid arthritis than the 15 GT repeat variation, which is the dominant phenotype in healthy controls. However, it appears that this allelic variation did not affect the STAT6 transcriptional activity. Interestingly, treatment with a DNA methyltransferase inhibitor markedly increased the expression of STAT6 mRNA and protein in human primary T cells. In contrast, IFN-gamma treatment significantly repressed the STAT6 transcriptional activity. Therefore, the present study provides insight into the molecular basis of STAT6 expression, and in particular, demonstrates that STAT6 expression is associated with DNA hypermethylation rather than promoter polymorphisms or allelic variations.

Summary Identification of the genes and polymorphisms underlying quantitative traits, and understanding how these genes and polymorphisms affect economic traits, are important for successful marker-assisted selection and more efficient management strategies in commercial cattle populations. Signal transducer and activator of transcription 6 (STAT6) gene is tightly connected to IL-4 and IL-13 signalling and plays a key role in TH2 polarization of the immune system. In addition, STAT6 acts as a mediator of leptin signalling and has been associated with body weight regulation. The objective of this study was to determine if SNPs within the bovine STAT6 gene are associated with economically important traits in feedlot cattle. The approach consisted of resequencing STAT6 using a panel of DNA from unrelated animals of different beef breeds. Specifically, 16 kb of STAT6 was resequenced in 47 animals and the process revealed 39 SNPs. From the 39 SNPs, a panel of 15 tag SNPs was genotyped in 1500 beef cattle samples with phenotypes to perform a marker-trait association analysis. Among the 15 tag SNPs, five and six were polymorphic in Bos taurus and Bos indicus respectively. An association analysis was performed between the 15 tag SNPs and 14 performance and production traits. SNP ss115492459:C > A, ss115492461:A > G and ss115492458:G > C were significantly associated with back fat, calculated yield grade, cutability, hot carcass weight, dry matter intake, days on feed, back fat rate and average daily gain. These three SNPs were present in all Bos taurus beef breeds examined. Our results provide evidence that polymorphisms in STAT6 are associated with carcass and growth efficiency traits, and may be used for marker-assisted selection and management in feedlot cattle.

Background and Aims: The signal transducer and activator of transcription 6 (STAT6) gene is located on chromosome 12q13.3–14.1 just within the IBD2 region and is a key transcription factor involved in interleukin (IL)-4 and IL-13-mediated Th2 response. The aim of the present study was to determine distribution of the STAT6 gene polymorphism in Chinese patients with ulcerative colitis. Methods: The G2964A polymorphism in the 3′ untranslated region of the STAT6 gene was studied in 84 unrelated Chinese patients with ulcerative colitis and 176 healthy controls by PCR and the amplification created restriction site method. The results were then compared with those from a Dutch study published previously. Result: Significant differences in genotype and allele frequencies of the STAT6 G2964A polymorphism were not found between patients with ulcerative colitis and healthy controls. Subgroups of the patients with ulcerative colitis classified according to the age at onset, sex and location of disease did not differ significantly in the distribution of this polymorphism. However, the genotypes (P

The Stat6 (signal transducer activator of transcription) gene is essential for the production of IL-4 an U 13, two cytokines that govern the activation of CD4+ T helper type 2 (Th2) cells. We hypothesized that mice with a deleted Stat6 gene (Stat6(exp -/-)) would have enhanced tumor immunity because they would preferentially make tumor-reactive Th1 cells, which are thought to facilitate the activation of CD8+ cytotoxic T cells (Tc), thereby improving tumor-specific immune responses. Our preliminary results demonstrate that tumor immunity to a metastatic mammary carcinoma is enhanced in the absence of the Stat6 gene. Although additional experiments demonstrated that tumor rejection in Stat64 mice is immunologically mediated by CD8+ T lymphocytes, this effect is not due to an improved Th1 response. Therefore, elimination of the Stat6 gene is a potent strategy for enhancing rejection of mammary cancer cells; however, the mechanistic explanation for the improved tumor immunity is no clear. The purpose of this project is to determine the potency of the Stat6 effect for enhancing immunity to metastatic mammary carcinoma, and to, identify the mechanism underlying the improved immunity. These experiments will not only provide insight into regulation of anti-tumor immunity but may also suggest novel approaches for enhancing anti-tumor immune responses.

We have identified a novel single nucleotide polymorphism at position 2964 (G/A) in the 3' untranslated region of the human STAT6 gene (GeneBank Accession No. U16031). A novel PCR-RFLP method has been devised for this polymorphism using the amplification-created restriction site (ACRS) method. Allele frequencies in the UK Caucasian population were found to be 0.33 for allele A and 0.67 for allele G.

Background Signal transducers and activators of transcription 6 (Stat6) is involved in the interleukin (IL)-4 and IL-13 signaling pathway. The aim of the present study was to evaluate whether polymorphisms in the 5′-flanking region of the Stat6 gene are associated with allergic diseases in Japanese children. Methods The Stat6 gene polymorphisms were genotyped by polymerase chain reaction (PCR) fragment length polymorphism analysis and the IL-4 receptor Ile50Val polymorphism was examined using PCR methods. Results Novel dinucleotide repeat polymorphisms were found in the 5′-flanking sequences, positioning at −865 (Pro A) and −690 (Pro B) of the Stat6 gene starting codon. The GT repeats in the 5′-flanking sequences were highly polymorphic (Pro A: 14–29 repeats; ProB: 14–20 repeats) with no significant differences in the frequency of allelic and genotypic distributions observed between allergic subjects and controls. In the GT repeat polymorphism of Stat6 exon 1, there was a significant difference in the frequency of genotypic distribution between the two groups (P = 0.003). The Stat6 exon 1 variant had significant linkage disequilibrium with Pro B variants, but not with Pro A. The GT repeat polymorphism was not associated with the IL-4 receptor Ile50Val polymorphism. Conclusions Variants of the Stat6 gene may be useful markers for predicting allergic diseases in Japanese children.