title: Foxp3 gene polymorphisms and haplotypes associate with susceptibility of Graves' disease in Chinese Han population.
abstract: BACKGROUND
  Foxp3 plays important roles in the pathogenesis of autoimmune diseases. To investigate the association between Foxp3 gene polymorphisms and the susceptibility to Graves' disease (GD) in Chinese Han population, four single nucleotide polymorphisms (SNPs) including -2383, -3279, -3499 in the promoter and IVS9+459 in the intron were genotyped.
  
  
  METHODS
  Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 GD patients and 306 healthy controls. The relative expression level of Foxp3 gene was measured by qRT-PCR.
  
  
  RESULTS
  The frequencies of AA/CA genotype of -3279 and CC genotype of IVS9+459 were significantly higher in GD patients than healthy controls. The AA/CA genotype of -3279 in female GD patients was more frequent than the male. For -3279, GD patients with higher TSH level or/and lower TRAb level were more frequent to carry A allele. We further analyzed the haplotypes of three SNPs and found that the haplotype CCA played a protective role in the susceptibility to GD. In contrast, the CAA and TCA haplotypes were associated with an increased susceptibility to GD. In addition, the mutation from C to A at the position of -3279 reduced the relative luciferase activity of Foxp3 promoter and decreased the expression of Foxp3 in GD patients.
  
  
  CONCLUSIONS
  Our findings indicated that Foxp3 functional polymorphisms and haplotypes in promoter were associated with the susceptibility to GD in Chinese Han population.
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China.
authors.forename: XiaoBei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Medicine, Chinese People's Liberation Army General Hospital, Postgraduate Medical School, Beijing, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Cai
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, PR China. Electronic address: lihuahu2013@163.com.
authors.forename: LiHua
authors.initials: L
authors.lastname: Hu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Foxp3; Graves' disease; Regulatory T cell; Single nucleotide polymorphism