FOXP3 Polymorphisms Research Articles

Association between FOXP3, FOXE1 Gene Polymorphisms and Risk of Differentiated Thyroid Cancer in Chinese Han Population

Background: Thyroid transcription factor gene (FOXE1) and Foxp3 play important roles in autoimmune and inflammatory disease as well as human malignancies. We aimed to investigate the association of FOXE1 and Foxp3 polymorphism with the susceptibility to differentiated thyroid cancers (DTC). Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 350 DTC patients and 306 healthy controls. Results: AA/AG genotype of FOXE1-rs1867277 and AA/AC genotype of Foxp3-rs3761548 were associated with a higher risk of DTC. The frequency of Foxp3-rs2280883 CC/CT genotype was lower in DTC patients. Besides, the AA/AC genotype of rs3761548 was more frequent in female DTC than the male. We further analyzed the association between 3 single nucleotide polymorphisms (SNPs) and DTC. We found that rs3761548 AA/AC genotype was more frequent in severe DTC patients (tumor diameter >1 cm) compared with the relative tender DTC patients (tumor diameter <1 cm). On the contrast, the frequency of rs2280883 CC/CT genotype was lower in severe DTC patients. Conclusion: Our findings suggested that FOXE1 and Foxp3 polymorphism were associated with the risk of DTC in Chinese Han population. Besides, rs3761548 AA/CC genotype was a potential risk factor for the susceptibility to DTC and rs2280883 CC/CT was a protective factor.

A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behçet's Disease in an Iranian Population

Background: Behçet's Disease (BD) is a rare autoimmune disease that involves the dysfunction of regulatory T cells. FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent studies have shown SNPs in the FOXP3 contribute to the susceptibility to some autoimmune disorders. To clarify the association between the FOXP3 gene and the risk of BD, 50 patients diagnosed with BD and 50 healthy controls from north-western Iran were genotyped by PCR-RFLP (Mun I and Pst I) for two SNPs including rs3761547 (-3499T/C) and rs3761548 (-3279 C/A) in the promoter region of the FOXP3 gene. In addition, a 506 bp nucleotide sequence of FOXP3 promoter was analyzed. The allele -3279 C/A was significantly associated with BD [p = 0.002; odds ratio (OR) = 3.841; 95% confidence interval (CI) 1.610 - 9.161]; whereas, there was no contribution of the FOXP3 polymorphism -3499T/C to BD [(p = 0.084); (OR = 0.348, 95% CI = 0.101 - 1.195)]. Meanwhile, sequence analysis showed 100% similarity in both controls and BD patient groups. Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behçet's disease among the north-western Iranian population.

Association of Foxp3 Polymorphism With Allograft Outcome in Renal Transplantation.

Association of Foxp3 Polymorphism With Allograft Outcome in Renal Transplantation.

Correction: Foxp3 (−/ATT) Polymorphism Contributes to the Susceptibility of Preeclampsia

Institutional affiliation 1 for authors Ximing Chen and Jianhua Xiao is incorrect. The correct affiliation is: 1. Medical College of University of South China， Hengyang, China. In addition, the Corresponding Author for the article was incorrectly listed as Ximing Chen. The Corresponding Author is Jianhua Xiao, who can be reached at JianhuaXia2010@163.com

Association of FoxP3/Scurfin Germline Polymorphism (C-2383T/rs3761549) with Colorectal Cancer

Background: FoxP3 gene encodes a transcription factor with crucial roles in the development and function of regulatory T cells. Objectives: The present study was conducted to investigate whether the C-2383T (rs3761549) polymorphism in the promoter region of the FoxP3 gene is associated with colorectal cancer. Patients and Methods: The study groups consist of 108 patients (52 men and 56 women) with colorectal cancer and 187 (126 men and 61 women) healthy individuals. They were genotyped for the FoxP3 polymorphism at position -2383 C >T using polymerase chain reactionrestriction fragment length polymorphism method. Frequencies of the gene variants were analyzed separately in men and women since FoxP3 is an X-linked gene. Results: The numbers of female patients with C/C, C/T and T/T genotypes were 48 (85.7%), 7 (12.5%) and 1 (1.8%), while in female controls, they were 53 (86.9%), 8 (13.1%) and 0 (0%), respectively. In male patients and controls, frequencies of the C genotype were 49 (94.2%) and 118 (93.7%), and the T genotype were 3 (5.8%) and 8 (6.3%), respectively. Genotype frequencies were not significantly different between controls and colorectal cancer patients. Distance metastasis was significantly associated with the FoxP3 polymorphism as calculated using Pearson’s chi-squared test (P = 0.006 in men and P = 0.03 in women). While 50% of metastatic patients had T or C/T (or T/T) genotype, the percentage of this genotype in non-metastatic patients was 4% in men and 11.5% in women. However, P values did not remain significant if differences were calculated using two-sided Fisher׳s exact test (P = 0.11 in men, and P = 0.09 in women); this might be due to the low number of our metastatic patients. Other characteristics of patients including age, tumor grade and stage were not significantly associated with the polymorphism. Conclusions: Our results supported an association between C-2383T FoxP3 polymorphism and metastatic colorectal cancer in southern Iran.

Genetic polymorphisms of FOXP3 in Italian patients with systemic sclerosis

A case control study to evaluate the possible influence of FOXP3 polymorphisms (rs3761548 and rs2280883) in the susceptibility of systemic sclerosis in an Italian Caucasian population. Subgroup analysis was also performed to test association between these SNPs and specific disease phenotypes. The study groups consisted of 467 individuals: 228 patients (194 with limited cutaneous form and 34 with diffuse cutaneous form of the disease) and 239 healthy control subjects. Genotyping was performed by high resolution melting analysis. Genotype distribution and allele frequency of the FOXP3 polymorphisms were analyzed statistically, using χ2 or Fisher exact test.Single-marker analysis of allelic and genotype frequencies revealed that SNP rs3761548 was not associated with systemic sclerosis susceptibility.Analysis of genotype and allele distributions of the rs2280883 genetic variant was associated, only in female subjects with systemic sclerosis, its limited subtype, and anti-centromere autoantibodies. Although these findings require replication in a larger set and other populations, FOXP3 rs2280883 may represent a novel susceptibility locus for systemic sclerosis in female subjects.

Foxp3 (−/ATT) Polymorphism Contributes to the Susceptibility of Preeclampsia

ObjectiveTo evaluate the potential influence of Foxp3 polymorphism on preeclampsia (PE) susceptibility, we conducted a case-control study in Han Chinese women.Methods Foxp3 genotyping was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 156 PE patients and 252 age-frequency matched controls. Immunohistochemical staining was used to detect the expression of Foxp3 specific transcription factor in 30 PE and 30 normal pregnant women.ResultsThe positive rate of Foxp3 expression in PE (26.67%) was significant difference from that in normal control (63.33%, P<0.05). The frequency of Foxp3-6054 TT genotype was significantly lower in PE patient than that in control. No significant difference was found in Foxp3-3279 genotypes between PE and control, as well as for the variant allele. The frequency of Foxp3-6054A/−3279C haplotype in PE was significantly higher than that in control (P<0.01), while the frequency of Foxp3 6054T/−3279C haplotype was significantly lower in PE patient than that in control (P<0.01).ConclusionOur findings suggest that the immune suppression function in PE patients is weakened, which may result in the occurrence of PE. Foxp3 polymorphism (rs5902434) may be a potential contributor for the development of PE in Han Chinese women.

Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases

The FOXP3 gene encodes a transcription factor thought to be important for the development and function of regulatory T cells (Treg cells). These cells are involved in the regulation of T cell activation and therefore are essential for normal immune homeostasis. Signals from microenvironment have a profound influence on the maintenance or progression of diseases. Thus, Tregs have an important marker protein, FOXP3, though it does not necessarily confer a Treg phenotype when expressed. FOXP3 polymorphisms that occur with high frequency in the general populations have been studied in common multifactorial human diseases. Dysfunction of FOXP3 gene product could result in lack of Treg cells and subsequently chronically activated CD4+ T cells which express increased levels of several activation markers and cytokines, resulting in some autoimmune diseases. In contrast, high Treg levels have been reported in peripheral blood, lymph nodes, and tumour specimens from patients with different types of cancer. The present study discusses the polymorphisms located in intron, exon and promoter regions of FOXP3 which have already been investigated by many researchers. FOXP3 has received considerable attention in attempts to understand the molecular aspect of Treg cells. Therefore, in the present study, the relationship between genetic polymorphism of FOXP3 in Treg-cell role and in disease development are reviewed considering the interactive effect of genetic factors.

FOXP3 genetic variant and risk of acute coronary syndrome in Chinese Han population

Coronary artery disease is the most common type of heart disease and a leading cause of morbidity and mortality all over the world. Acute coronary syndrome (ACS) is the most serious form of coronary artery disease. Recently, many studies indicated that genetic susceptibility may play a vital role in the pathogenesis of coronary heart disease including ACS. Forkhead/winged helix transcription factor (FOXP3) gene polymorphisms have been previously found to be associated with inflammatory diseases. To determine whether FOXP3 polymorphisms are associated with ACS, we examined the single nucleotide polymorphism rs3761548 of FOXP3 gene by polymerase chain reaction-polyacrylamide gel electrophoresis in 226 ACS patients and 259 unrelated healthy subjects. Our results showed that single nucleotide polymorphism rs3761548 had association with ACS in Chinese Han population. These data indicate that, for the first time, FOXP3 gene polymorphism may appear to play an important role in the susceptibility of ACS in Chinese Han population.

Genetic association of FOXP3 gene polymorphisms with allograft rejection in renal transplant patients

FOXP3 gene is known to be important for regulatory T cell development and function, and is associated with the rejection of human kidney transplants. The present study was therefore conducted to determine the effect of FOXP3 polymorphisms on allograft rejection in renal transplant recipients. A total of 166 adult patients were categorized into either a Rejection group (65 patients) or a No rejection group (101 patients). Rs3761547, rs3761548 and rs2232365 variant alleles in the FOXP3 gene were genotyped using a TaqMan probe technique, and their relationships with rejection were investigated. There was no significant difference in the genotype frequencies of rs3761547 and rs2232365 variants between patients with and without rejection history (P > 0.05). Binary logistic regression analysis showed that the rs3761548 AA genotype carriers were associated with about a fourfold greater risk for rejection compared with CC genotype (5 years post-transplant: odds ratio 3.95, 95% confidence interval 1.27-12.29, P = 0.018). Kaplan-Meier analysis revealed a lower mean time to the first rejection in rs3761548 AA compared with CC genotype patients (Log rank = 4.303, P = 0.038). Multivariate Cox regression analysis indicated that rs3761548 AA genotype carriers have up to about a twofold (hazard ratio 2.37, 95% confidence interval 1.17-4.80, P = 0.017) higher risk for rejection than CC carriers. Our study suggests an association between FOXP3 rs3761548 polymorphisms and allograft rejection in renal transplantation. This association should be further proven in large prospective studies because of the small sample size and confounding factors in this retrospective study.

Genetic association study of polymorphisms FOXP3 and FCRL3 in women with endometriosis

To consider a possible cumulative effect of two genetic polymorphisms (FOXP3 C-2383T/rs3761549 and FCRL3 C-169T/rs7528684) that were previously shown to be associated with endometriosis. Genetic association study. Human reproduction outpatient clinic of Faculdade de Medicina do ABC. One hundred eighty-eight infertile women with endometriosis and 169 controls. Detection of polymorphisms FOXP3 (C-2383T/rs3761549) and FCRL3 (C-169T/rs7528684) by TaqMan real-time polymerase chain reaction. The results were analyzed statistically. Genotype distribution, allele frequency, and combination analysis of the FOXP3 and FCRL3 polymorphisms. Single-marker analysis revealed a significant association of FOXP3 C-2383T and FCRL3 C-169T, independently, with endometriosis-related infertility, regardless of the stage of the disease. Considering the combined genotypes of FCRL3 and FOXP3 polymorphisms, a positive association was found between genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT and the risk of endometriosis development. Moreover, a progression of the disease risk was observed according to the presence of one or two copies of risk allele FCRL3 C and only one copy of risk allele FOXP3 T (odds ratio [OR] = 2.14, OR = 3.25, and OR = 6.0, respectively, for genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT). Our findings support a possible gene-gene interaction leading to a cumulative effect on endometriosis development.

Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplained recurrent spontaneous abortion

To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA). PCR-restriction fragment length polymorphism (rs3761548, rs2294021) and PCR with sequence-specific primers (rs2232365, rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. (1) The frequencies of rs3761548A/C were 10.3%, 22.3% in genotype C/C, 38.4%, 40.2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50.0% in genotype A/G, 46.6%, 34.8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference (P < 0.05). The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR = 1.73, 1.61;all P < 0.05). (2) There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls (P = 0.10), but the frequency of del allele in URSA was statistically increased than that of controls (71.2%, 62.5%;OR = 1.49, P = 0.04). (3) There was no different distribution in 3 genotypes (C/C, T/C, T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P = 0.18 and 0.08). (4) Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA (OR = 2.51, P < 0.01) but haplotype del-C-G and ATT-A-A could provide protection on URSA (OR = 0.18, 0.22; all P < 0.01). Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and (or) its expression.

Analysis of FOXP3 polymorphisms in infertile women with and without endometriosis

To evaluate FOXP3 polymorphisms (rs3761549, rs3761548, rs2232368, rs2232366, and rs2280883) in a group of infertile women with and without endometriosis and controls. Case control study. Human Reproduction Outpatient Clinic of Faculdade de Medicina do ABC. The study groups were 177 infertile women with endometriosis, 71 women with idiopathic infertility, and 171 fertile women as controls. The FOXP3 polymorphisms were identified by TaqMan polymerase chain reaction (PCR). The results were analyzed statistically. Genotype distribution, allele frequency, and haplotype analysis of the FOXP3 polymorphisms. Single-marker analysis revealed that FOXP3 rs3761549 was significantly associated with endometriosis. In the infertile group without endometriosis, single-marker analysis revealed statistical difference for rs2280883 and rs2232368 FOXP3 polymorphisms. No associations were found with rs3761548 and rs2232366 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five FOXP3 polymorphisms identified a haplotype CTTGA associated with endometriosis and ACTAG associated with idiopathic infertility. This is the first study to report an association between FOXP3 polymorphisms and endometriosis and/or infertility. These findings require replication in other populations but suggest that the FOXP3 polymorphisms can be associated with risk of idiopathic infertility (rs2280883 and rs2232368) and endometriosis (rs3761549) in Brazilian women.

RETRACTED ARTICLE: Foxp3 rs2294021 polymorphism contributes to the susceptibility to breast carcinoma

Objective Foxp3, the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women.

Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients

Psoriasis is a common dermatological disorder, in which autoimmunity plays an important role. CD4(+)CD25(+) regulatory T cells (T-regs) have been suggested to be involved in the pathogenesis of some autoimmune diseases. T-regs express the fork head/winged helix transcription factor, FOXP3, which appears to be of key importance in the development and function of T-regs. Studies have found that single-nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to susceptibility to some autoimmune disorders. However, information about FOXP3 gene in psoriasis is limited. This study evaluated the association between FOXP3 gene SNPs and susceptibility to psoriasis in a Han Chinese population. In a hospital-based case-control study, 524 patients with psoriasis and 549 psoriasis-free controls were recruited according to age and gender. We investigated four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/G; IVS9+459, A/G) in psoriatic patients, and assessed allele and genotype frequencies in psoriatic patients (237 females, 287 males) and normal controls (272 females, 277 males). The polymorphisms were genotyped using the PCR sequence-specific primer (PCR-SSP) technique and PCR-restriction fragment length polymorphism (RFLP) analysis. We found that increased risk of psoriasis was associated with the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01-1.74) and the combined AC+AA genotype (adjusted OR, 1.38; 95% CI, 1.07-1.78), compared with the -3279 CC genotype. We also found that an increased risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype (adjusted OR, 2.24; 95% CI, 1.41-3.58). However, the combined GA+GG genotype showed no such tendency (adjusted OR=1.28; 95% CI, 1.00-1.64), compared with the IVS9+459 AA genotype. There was no evidence of an increased risk associated with the FOXP3-6054 deletion/ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the FOXP3-3279 AC+AA genotype was more obviously associated in males (adjusted OR=1.60, 95% CI=1.11-2.31) and severe psoriasis patients (PASI score >20; adjusted OR=1.97, 95% CI=1.41-2.75). Meanwhile, the FOXP3 IVS9+459 GA+GG genotype was also associated with severe psoriasis patients (adjusted OR=1.69, 95% CI=1.21-2.36). FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a Han Chinese population. Larger studies are needed to confirm these findings.

Genetic association study of FOXP3 polymorphisms in allergic rhinitis in a Chinese population

The FOXP3 gene encodes a transcription factor thought to be essential for the development and function of regulatory T cells, which are prevailing mediators of immunological tolerance via suppression/modulation of both T helper (Th)-1 and Th-2 mediated immune responses. Previous studies have demonstrated an association between common polymorphisms in FOXP3 and a number of immune diseases. The aim of this study was to investigate whether genetic polymorphisms at the FOXP3 locus predispose to allergic rhinitis (AR) in a Chinese Han population. Six polymorphisms in promoter and intron areas were genotyped in 193 AR subjects and 191 healthy controls. Twelve exons were also analyzed among cohorts of 157 AR patients and 118 healthy controls. Whole-population and gender strata analyses revealed that no single nucleotide polymorphisms in FOXP3 were identified as significantly associated with AR. Regarding the stratified analysis for heterozygotes and homozygotes, the heterozygous allele in rs3761548 ( p = 0.020, OR Het = 3.12) appeared significant. Subgroup analysis for the presence of different allergen allergies also demonstrated a significant association for house dust mites (rs3060515, p = 0.010, odds ratio (OR) = 2.18; rs3761547, p = 0.013, OR = 2.00). Additionally, no polymorphisms in coding regions contributing to a susceptibility to AR were noted. Our study provides the first evidence for the association of the FOXP3 polymorphism with AR in a Chinese population.

FOXP3 Polymorphism and gene expression in Italian patients with Kawasaki Syndrome

Materials and methods The single nucleotide polymorphism (SNP) at position 543 of exon 5 of FOXP3 was investigated in 58 caucasian children patients with KS (F:30, M:28), recruited at our Paediatric Reumatology Unit. In 6 patients we could evaluate the percentage of circulating CD4+ T cells co-expressing CD25 and FOXP3 by flow cytometry, mRNA transcripts of FOXP3 in PBMCs by Real Time PCR (with Rnase P as internal control gene), and the levels of IL-17 in PBMCs supernatants (5 × 104 cells) by a quantitative immunoassay Kit.

347: Correlation Between FOXP3 Gene Polymorphisms in Donors, and the Severity of Acute Graft-Versus-Host Disease in Patients after Related Allogeneic Stem Cell Transplantation

INTRODUCTION: Acute Graft-versus-host disease (aGVHD) is a major complication of allogeneic stem cell transplantation (alloSCT). Risk factors include patient age, sex matching, CMV status and degree of match. Regulatory T cells are critical for immune tolerance processes such as aGVHD, and express the transcription factor FOXP3, a member of the forkhead/winged-helix family, identified as a key regulatory gene required for the development and activity of these cells. It has been suggested that genetic expression of FOXP3 is inversely correlated with the severity of the GVHD. We studied donor’s DNA looking for 5 polymorphisms on the promoter region of the FOXP3 gene, and we tried to correlate them with presence and degree of aGVHD. PATIENTS AND METHODS: We studied donors of stem cells for allogeneic stem cell transplants. We looked for the presence of the following polymorphisms by PCR: POL01 –5906 T/A rs2869211; POL03 –3279 A/C rs3761548 ; POL04 –2383 C/T rs3761549 ; POL05 –1383 C/T rs2232364 ; POL06 –924 A/G rs2232365. RESULTS: Our sample consisted of 31 donors, all siblings. In them we found only 2 of the 5 FOXP3 polymorphisms, either as homozygous or heterozygous. These polymorphisms were found in 15/31 donors, with 12 being homozygous (38.7%), and 3 heterozygous (9.7%). These genes polymorphisms were POL03 y POL06. The most observed polymorphism was POL-06 with 9 cases, while POL-03 was found in 6 donors. Only sex difference and CMV status had an elevated hazard ratio for developing GVHD (HR=1.18, CI95%: 0.18 to 7.64; p=0.85) and (HR=3.0, CI95%: 0.07 to 126; p=0.46) respectively. We found no statistically significant difference in the incidence of GVHD between patients who had received cells from donor with or without a FOXP3 polymorphism (p=0.87). When we analyzed the risk of presenting GVHD, results suggest that having one of the 2 positive polymorphisms of the FOXP3 gene could have a protective effect for the patient. For POL03 HR=0.87, CI95%:0.18 to 4.14; p=0.86, and for POL06, HR=1, CI95%: 0.37 to 2.64, p=0.67. CONCLUSIONS: Even though our sample is still small to make conclusive remarks, we believe that our results point toward some level of protection from acute GVHD in patients receiving cells from donors expressing POL03 and POL06. It is also worthwhile mentioning the relatively high frequency of these polymorphisms, as well as the absence of the other 3. absence of the other 3. Footnotes Disclosure: No relevant conflicts of interest to declare. CiteULike Connotea Delicious Digg Facebook Reddit Technorati Twitter What's this? Copy right © 2007 by American Society of Hematology Online ISSN: 1528-0020

Correlation between FOXP3 Gene Polymorphisms in Donors, and the Severity of Acute Graft-Versus-Host Disease in Patients after Related Allogeneic Stem Cell Transplantation.

INTRODUCTION: Acute Graft-versus-host disease (aGVHD) is a major complication of allogeneic stem cell transplantation (alloSCT). Risk factors include patient age, sex matching, CMV status and degree of match. Regulatory T cells are critical for immune tolerance processes such as aGVHD, and express the transcription factor FOXP3, a member of the forkhead/winged-helix family, identified as a key regulatory gene required for the development and activity of these cells. It has been suggested that genetic expression of FOXP3 is inversely correlated with the severity of the GVHD. We studied donor's DNA looking for 5 polymorphisms on the promoter region of the FOXP3 gene, and we tried to correlate them with presence and degree of aGVHD.PATIENTS AND METHODS: We studied donors of stem cells for allogeneic stem cell transplants. We looked for the presence of the following polymorphisms by PCR: POL01 −5906 T/A rs2869211; POL03 −3279 A/C rs3761548 ; POL04 −2383 C/T rs3761549 ; POL05 −1383 C/T rs2232364 ; POL06 −924 A/G rs2232365.RESULTS: Our sample consisted of 31 donors, all siblings. In them we found only 2 of the 5 FOXP3 polymorphisms, either as homozygous or heterozygous. These polymorphisms were found in 15/31 donors, with 12 being homozygous (38.7%), and 3 heterozygous (9.7%). These genes polymorphisms were POL03 y POL06. The most observed polymorphism was POL-06 with 9 cases, while POL-03 was found in 6 donors. Only sex difference and CMV status had an elevated hazard ratio for developing GVHD (HR=1.18, CI95%: 0.18 to 7.64; p=0.85) and (HR=3.0, CI95%: 0.07 to 126; p=0.46) respectively. We found no statistically significant difference in the incidence of GVHD between patients who had received cells from donor with or without a FOXP3 polymorphism (p=0.87). When we analyzed the risk of presenting GVHD, results suggest that having one of the 2 positive polymorphisms of the FOXP3 gene could have a protective effect for the patient. For POL03 HR=0.87, CI95%:0.18 to 4.14; p=0.86, and for POL06, HR=1, CI95%: 0.37 to 2.64, p=0.67.CONCLUSIONS: Even though our sample is still small to make conclusive remarks, we believe that our results point toward some level of “protection” from acute GVHD in patients receiving cells from donors expressing POL03 and POL06. It is also worthwhile mentioning the relatively high frequency of these polymorphisms, as well as the absence of the other 3.

The regulatory T cell gene FOXP3 and genetic susceptibility to thyroid autoimmunity: An association analysis in Caucasian and Japanese cohorts

FOXP3 is a key gene in the development of regulatory T cells (Treg). FOXP3 expression commits naïve T cells to become Treg cells. Indeed, mutations in the FOXP3 gene cause severe systemic autoimmune diseases in humans and in mice. Therefore, we hypothesized that the FOXP3 gene may be associated with thyroid autoimmunity which is among the typical autoimmune diseases that develop in individuals with FOXP3 mutations. Moreover, the FOXP3 gene is located within an X-chromosome locus (Xp11.23) previously shown to be linked with autoimmune thyroid diseases (AITD). We tested the FOXP3 gene locus for association with AITD in two large cohorts of US Caucasians and Japanese AITD patients. We analyzed 269 Caucasian AITD patients (52 males and 217 females) and 357 Caucasian controls (159 males and 198 females), as well as 377 female Japanese AITD patients and 179 female Japanese controls. The FOXP3 gene locus was analyzed using four microsatellite polymorphisms [(GT)n; (TC)n; DXS573; DXS1208] flanking the FOXP3 gene locus. Interestingly, while no association was found between FOXP3 polymorphisms and AITD in the Japanese cohort there was a significant association in the Caucasian cohort. There was a significant association of the (TC)n polymorphism with AITD in the Caucasian male AITD patients ( p = 0.011; 5 degrees of freedom [df]). Similarly, there was an association between the DXS573 microsatellite and AITD in the Caucasian female AITD patients ( p = 0.00023; 4 df). These results suggest that polymorphisms of the FOXP3 gene may play a role in the genetic susceptibility to AITD in Caucasians, perhaps by altering FOXP3 function and/or expression.