101. Synergistic combined effect between CD40-1CT and CTLA-4+6230GA polymorphisms in Graves' disease
- Author
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Zhuoqing Hu, Meilian Liu, Liwen Bao, Shuo Fang, Meifen Wu, Wei Li, Ping Wu, Xiaoming Chen, Ge Wu, Wei Xiong, and Manyang Chen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Graves' disease ,Single-nucleotide polymorphism ,Trab ,Biology ,Polymorphism, Single Nucleotide ,Young Adult ,Gene Frequency ,Internal medicine ,Genotype ,Genetics ,medicine ,Humans ,CTLA-4 Antigen ,Allele ,CD40 Antigens ,Allele frequency ,Epistasis, Genetic ,General Medicine ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Graves Disease ,Genotype frequency ,Endocrinology ,CTLA-4 ,Case-Control Studies ,Immunology ,Female ,Genome-Wide Association Study - Abstract
The aim of this study was to investigate whether a genetic combined effect exists between CD40-1CT and CTLA-4+6230GA (CT60) polymorphisms and whether the combined effect renders susceptibility to Graves' disease (GD). We recruited 260 patients with GD and 248 healthy controls. Single nucleotide polymorphisms were genotyped by polymerase chain reaction-high resolution melting. Genetic polymorphisms related to GD were identified, levels of thyroid stimulating hormone receptor antibodies (TRAb) were measured, and genetic interactions were assessed by logistic regression analysis. Significant difference in allele and genotype frequency of CD40-1CT polymorphism was observed between the patients and control subjects (P0.001, 0.002 respectively). As for CTLA-4+6230GA polymorphism, significant difference was observed only in allele frequencies between the patient and control groups (P=0.014). Moreover, a significant combined effect was presented in CD40-1CT and CTLA-4+6230GA polymorphism (P=0.020), and all, but one, combination CC-genotype of CD40-1CT and GG-genotype of CTLA-4+6230GA polymorphism has 54% lower risk of GD development than subjects with the CC and GG genotypes (OR=0.46, 95% CI=0.25-0.84). In newly onset GD group, neither single SNP (CD40-1CT or CTLA-4+6230GA polymorphism) nor their combined effect was showed a significant association with TRAb concentration (all P0.05). Our findings suggest a possible additive combined effect between CD40-1CT and CTLA4+6230GA polymorphisms in the development of GD.
- Published
- 2014