Study On The Relationship Between FOXP3 Gene Polymorphism And Alopecia Areata

Background and objective:Alopecia Areata(AA)is a kind of chronic inflammatory disease with the characteristic symptom of hair loss. It is characterized by a sudden onset of non-scarring, circumscribed bald patches,that may increase in numbers and coalesce to form extensive alopecia areata, affecting people of both sexes and of all ages. Both the accurate etiology and the pathogenesis of alopecia areata are still unclear, which might involve Genetic susceptibility, immune dysfunction, neuropsychological factors and environmental factors and so on. However, research has shown that alopecia areata is an organ-specific autoimmune diseases,T lymphocytes in the pathogenesis of alopecia areata play an important role. It was in the late 1950s that an autoimmune mechanism was proposed for alopecia areata. Since then, enough circumstantial evidence has accumulated to support such a proposition.Some study confirmed that hair follicle dysfunction in alopecia areata is T cell-mediated immune dysfunctions. The possible mechanism is that under the circumstances of the genetic and environmental factors, excessive hair follicle antigens released resultting in overloaded self-antigens, abnormal activation of autoreactive lymphocytes,and start the Th1 cytokine response pattern-based immune response.In more than 10 years of experiments using a severe combined immunodeficiency (SCID) mouse model of human AA, Kalish and Gilhar[1]have clearly demonstrated that AA is an autoimmune disease mediated by T lymphocytes in which autoantigens are necessary to activate T cells that induced the occurrence of AA. Many Similar experenments have showed both CD4 and CD8 T cells play key roll during the occurrence of alopecia areata ,and the CD8 cells is more important. However, the role can not be ignored that the significant reduction of CD4 + CD25 + T cells in the incidence of AA.The study from McElwee et al showed that the perifollicular infiltrates of T cells in the AA affected epithelium are dominated by CD4+T cell , also accompany with CD8+T cell, which participate in the progress of AA together. Zoller et al study the alopecia areata in C3H/HeJ mouse show that CD8+T is a key factor in the pathogenesis of AA, CD4+CD25-T cell may relate with diffuse and systematic alopecia, and CD4+CD25+T cell is an important regulatory factor .In addition, a large number of clinical and laboratory data show that, in addition to T cells, the cell factor is also one of the key factors causing alopecia areata. The local infiltration of lymphocyte in hair follicles of alopecia areata often appear simultaneously with the increased cytokine expression, the increase of some cytokines contribute to the further activation and infiltration of lymphocytes.Current researchs are mainly on IL-1,IL-2,α-TNF,IFNγ,IL-4,IL-10 and so on.Foxp3 express specificly in Treg cell. The expression of the transcription factor Foxp3 have important significance in the maturation,development and inhabit function of Treg cell. Shimon Sakaguchi'studies have shown that the Foxp3 transcription factor lacked in some autoimmune diseases of human and small rodents could be expressed specificly in CD4 + T regulatory cell. In addition, the using of retroviral Foxp3 gene transformed into the non-activated T cells have the similar functions comparing with naturally occurring CD4 + regulatory T cells. The FOXP3 is essential for the development of Treg cell in the thymus gland. FOXP3 can be expressed in CD4+ CD25-T cell which can obtain the mark of Treg cell, inhibition function can be aquired by the over expressing of FOXP3 in CD4+CD25-T cell and CD8+T . FOXP3 is also involved in regulating the expression of cytokines, FOXP3 gene can inhibit the expression of cytokine IL-2, IL-4, IFN-γetc[7-8], while these regulatory T cells and cytokines played an important role in the occurrence and development of alopecia areata.It can be referred that the expression status of FOXP3 gene is involved in the pathogenesis of AA. In this study, we recruit Han population in Chongqing city to study the polymorphism sites(rs3761547,rs3761548)to investigate whether the FOXP3 gene polymorphisms was associated with the affectivity of alopecia areata(AA).Methods:To investigate whether the FOXP3 gene polymorphisms was associated with the occurrence or severity of alopecia areata(AA), 240 Chinese alopecia areata patients were consecutively recruited matched with 248 healthy subjects that have the same age,gender and race were included from the same geographical area as controls. Genomic DNA was taken with the blood extracted DNA extraction kit .SNPs(rs3761547,rs3761548)were defined for FOXP3 gene by using the data of Han population from the Hapmap homepage.PCR-RFLP was used for the genotyping and analyzing SNP by statistics. And the DNA sequencing was used to verify the accuracy of the genotype.Results:1,A significant difference of the three genotype at rs3761548 site was observed between patients and controls(P=0.015).2,No association was found at rs3761547 between AA and control group(P=0.12).3,Logistic aggression model analysis indicated that allele A of rs3761548 is associated with AA.4,Estimated haplotype frequency distributions of rs3761547 and rs3761548 showed that significant difference of the haplotype GA and GC between cases and controls.5,Logistic aggression model analysis indicated that haplotype GA is the danger factor(OR:3.2010 ; 95% CI:2.1538-4.7573),but haplotype GC is the protection factor(OR:0.4831;95% CI: 0.3577-0.6526).Conclusions:The rs3761548 genetic polymorphisms of FOXP3 gene may be associated with AA,It may be a risk factor of AA in Chinese Chongqing Han population. But there was no association between the rs3761547 and AA.