title: Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus.
abstract: OBJECTIVE
  Autophagy-related gene 5 (ATG5), ATG7, B-lymphoid tyrosine kinase (BLK) and B-cell scaffold protein with ankyrin repeats 1 (BANK1) are involved in B-cell signaling; several genome-wide association studies detected these genes as candidates involved in systemic lupus erythematosus (SLE). We aimed to replicate the association of these genes with SLE in Chinese Han and to search for possible gene-gene interactions.
  
  
  METHODS
  TaqMan single-nucleotide polymorphism (SNP) genotyping was used to detect rs548234, rs665791 in ATG5, rs11706903 in ATG7, rs2736340 in BLK and rs10516487 in BANK1 in 382 SLE patients and 660 healthy controls. The epistasis effect was analyzed by logistic regression, multifactor dimensionality reduction (MDR) and linear regression analysis.
  
  
  RESULTS
  SLE was associated with frequency of rs548234 (P = 0.010; odds ratio [OR] = 1.298), rs2736340 (P = 2.47 × 10-5; OR = 1.574) and rs10516487 (P = 0.002; OR = 0.642). Although no epistasis effects were found among three autophagy-related gene loci or with rs2736340 and rs10516487, BLK and BANK1 had the closest interaction effect on logistic regression analysis (P = 0.013; OR = 1.205), MDR (P < 0.0001), and linear regression analysis (P = 0.0017; R2= 0.1806). The risk genotype TT of rs2736340 was associated with decreased messenger RNA level of BLK; BLK transcript level was lower in SLE patients than healthy controls.
  
  
  CONCLUSIONS
  We confirmed the association of rs548234, rs2736340 and rs10516487 with SLE in Chinese Han and reinforced our hypothesis of their epistasis effect in regulating B-cell signaling in SLE.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.|Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dang
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Bian
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000276:immunology; D000328:Adult; D044466:Asian People / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000235:genetics* / Q000276:immunology; D000071193:Autophagy-Related Protein 7 / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction; D055815:Young Adult; D019061:src-Family Kinases / Q000235:genetics* / Q000276:immunology
chemical_list: C502778:ATG5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000071187:Autophagy-Related Protein 5; C447641:BANK1 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; C584409:BLK protein, human; D019061:src-Family Kinases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7
keywords: B-cell signaling; autophagy; genetic interaction; single-nucleotide polymorphisms; systemic lupus erythematosus