title: Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population.
abstract: OBJECTIVE
  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.
authors: Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, People's Republic of China. tlcool318@163.com.|School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People's Republic of China. tlcool318@163.com.
authors: Liang
authors: L
authors: Tang
authors: Department of Clinical Medicine, Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China.
authors: Pengcheng
authors: P
authors: Wan
authors: 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.
authors: Yong
authors: Y
authors: Wang
authors: 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.
authors: Jiabao
authors: J
authors: Pan
authors: School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People's Republic of China.
authors: Yan
authors: Y
authors: Wang
authors: 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.
authors: Bifeng
authors: B
authors: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D053634:TYK2 Kinase / Q000235:genetics*
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D053634:TYK2 Kinase; C070139:TYK2 protein, human
keywords: Gene–gene interaction; Han Chinese population; IRF5; Systemic Lupus Erythematosus (SLE); TYK2