Lei Zheng1, XiaoBei Wang1, Lijuan Xu2, Ning Wang1, Pengcheng Cai1, Tao Liang1, LiHua Hu3. 1. 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. 2. Department of Clinical Laboratory Medicine, Chinese People's Liberation Army General Hospital, Postgraduate Medical School, Beijing, PR China. 3. 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.
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. CONCLUSION: Our findings indicated that Foxp3 functional polymorphisms and haplotypes in promoter were associated with the susceptibility to GD in Chinese Han population.
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 GDpatients 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 GDpatients than healthy controls. The AA/CA genotype of -3279 in female GDpatients was more frequent than the male. For -3279, GDpatients 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 GDpatients. CONCLUSION: Our findings indicated that Foxp3 functional polymorphisms and haplotypes in promoter were associated with the susceptibility to GD in Chinese Han population.
Authors: Hyewon Park; Nuri Lee; Ji Won In; Eun Youn Roh; Kyoung Un Park; Sue Shin; Jaeseok Yang; Eun Young Song Journal: Ann Lab Med Date: 2017-09 Impact factor: 3.464
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