Jie Dang1,2, Jiangxia Li1, Qian Xin1, Shan Shan1, Xianli Bian1, Qianqian Yuan1, Na Liu1, Xiaochun Ma1, Yan Li1, Qiji Liu1. 1. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China. 2. Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan, Ningxia, China.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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 SLEpatients 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 SLEpatients than healthy controls. CONCLUSION: 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: Lorenzo Galluzzi; José Manuel Bravo-San Pedro; Beth Levine; Douglas R Green; Guido Kroemer Journal: Nat Rev Drug Discov Date: 2017-05-19 Impact factor: 84.694
Authors: S Udhaya Kumar; D Thirumal Kumar; R Siva; C George Priya Doss; Salma Younes; Nadin Younes; Mariem Sidenna; Hatem Zayed Journal: Front Bioeng Biotechnol Date: 2020-04-30
Authors: Simon H Jiang; Vicki Athanasopoulos; Julia I Ellyard; Aaron Chuah; Jean Cappello; Amelia Cook; Savit B Prabhu; Jacob Cardenas; Jinghua Gu; Maurice Stanley; Jonathan A Roco; Ilenia Papa; Mehmet Yabas; Giles D Walters; Gaetan Burgio; Kathryn McKeon; James M Byers; Charlotte Burrin; Anselm Enders; Lisa A Miosge; Pablo F Canete; Marija Jelusic; Velibor Tasic; Adrian C Lungu; Stephen I Alexander; Arthur R Kitching; David A Fulcher; Nan Shen; Todor Arsov; Paul A Gatenby; Jeff J Babon; Dominic F Mallon; Carmen de Lucas Collantes; Eric A Stone; Philip Wu; Matthew A Field; Thomas D Andrews; Eun Cho; Virginia Pascual; Matthew C Cook; Carola G Vinuesa Journal: Nat Commun Date: 2019-05-17 Impact factor: 14.919