Liang Tang1,2, Pengcheng Wan3, Yong Wang4, Jiabao Pan4, Yan Wang5, Bifeng Chen6. 1. Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, People's Republic of China. tlcool318@163.com. 2. School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People's Republic of China. tlcool318@163.com. 3. Department of Clinical Medicine, Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China. 4. Department of Biological Science and Biotechnology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, People's Republic of China. 5. School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People's Republic of China. 6. Department of Biological Science and Biotechnology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, People's Republic of China. cbifeng@whut.edu.cn.
Abstract
OBJECTIVES: The purpose of this case-control study was to investigate whether polymorphisms and gene-gene interactions of the two type I interferon (IFN) genes (IRF5 and TYK2) are the susceptible factors of systemic Lupus erythematosus (SLE) in the Han Chinese population. METHODS: The four variants [rs2004640, rs2070197, rs10954213 and exon6 insertion/deletion (in/de)] of IRF5 gene and five single-nucleotide polymorphisms (SNPs) (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 gene were examined in a cohort of 642 SLE patients and 642 healthy controls. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing in 10 % sample randomly. RESULTS: Rs2070197 was not polymorphic in this study, and was excluded in further analysis. Significant association was found for loci on IRF5 (rs2004640: p = 0.0003, p corr = 0.0012) and TYK2 (rs280500: p = 8.83 × 10(-6), p corr = 4.41 × 10(-5); rs2304256: p = 3.71 × 10(-6), p corr = 1.85 × 10(-5); rs8108236: p = 0.0004, p corr = 0.002), but not for other SNPs. Significant association was also observed for genotypes of IRF5 (rs2004640, p = 0.0009, p corr = 0.0036) and TYK2 SNPs (rs280500: p = 5.21 × 10(-5), p corr = 2.61 × 10(-4); rs2304256: p = 7.72 × 10(-6), p corr = 3.86 × 10(-5); rs8108236: p = 0.002, p corr = 0.01). Nevertheless, two haplotypes based on the 3 variants [exon6(in/de), rs10954213, rs2004640] of IRF5 (DAG and IAT) could define protective or susceptibility haplotype in SLE. Similarly, three haplotypes containing 5 SNPs (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 (GATAT, AGGAT and GAGGT) may also be associated with SLE in Han Chinese. Additionally, the gene-gene interaction analysis was conducted on the IRF5 and TYK2 SNPs. And a three-way interaction between TYK2 rs280500, rs2304256 and IRF5 rs10954213 and SLE was found (p < 0.0001). CONCLUSIONS: Genetic associations and gene-gene interactions of IRF5 and TYK2 were significantly detected in Han Chinese with SLE. Our results had important implications for future research on the role of type I IFN function in SLE susceptibility.
OBJECTIVES: The purpose of this case-control study was to investigate whether polymorphisms and gene-gene interactions of the two type I interferon (IFN) genes (IRF5 and TYK2) are the susceptible factors of systemic Lupus erythematosus (SLE) in the Han Chinese population. METHODS: The four variants [rs2004640, rs2070197, rs10954213 and exon6 insertion/deletion (in/de)] of IRF5 gene and five single-nucleotide polymorphisms (SNPs) (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 gene were examined in a cohort of 642 SLEpatients and 642 healthy controls. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing in 10 % sample randomly. RESULTS:Rs2070197 was not polymorphic in this study, and was excluded in further analysis. Significant association was found for loci on IRF5 (rs2004640: p = 0.0003, p corr = 0.0012) and TYK2 (rs280500: p = 8.83 × 10(-6), p corr = 4.41 × 10(-5); rs2304256: p = 3.71 × 10(-6), p corr = 1.85 × 10(-5); rs8108236: p = 0.0004, p corr = 0.002), but not for other SNPs. Significant association was also observed for genotypes of IRF5 (rs2004640, p = 0.0009, p corr = 0.0036) and TYK2 SNPs (rs280500: p = 5.21 × 10(-5), p corr = 2.61 × 10(-4); rs2304256: p = 7.72 × 10(-6), p corr = 3.86 × 10(-5); rs8108236: p = 0.002, p corr = 0.01). Nevertheless, two haplotypes based on the 3 variants [exon6(in/de), rs10954213, rs2004640] of IRF5 (DAG and IAT) could define protective or susceptibility haplotype in SLE. Similarly, three haplotypes containing 5 SNPs (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 (GATAT, AGGAT and GAGGT) may also be associated with SLE in Han Chinese. Additionally, the gene-gene interaction analysis was conducted on the IRF5 and TYK2 SNPs. And a three-way interaction between TYK2rs280500, rs2304256 and IRF5rs10954213 and SLE was found (p < 0.0001). CONCLUSIONS: Genetic associations and gene-gene interactions of IRF5 and TYK2 were significantly detected in Han Chinese with SLE. Our results had important implications for future research on the role of type I IFN function in SLE susceptibility.
Entities:
Keywords:
Gene–gene interaction; Han Chinese population; IRF5; Systemic Lupus Erythematosus (SLE); TYK2
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