Guo L, Deshmukh H, Lu R, Vidal G S, Kelly J A, Kaufman K M, Dominguez N, Klein W, Kim-Howard X, Bruner G R, Scofield R H, Moser K L, Gaffney P M, Dozmorov I M, Gilkeson G S, Wakeland E K, Li Q-Z, Langefeld C D, Marion M C, Williams A H, Divers J, Alarcón G S, Brown E E, Kimberly R P, Edberg J C, Ramsey-Goldman R, Reveille J D, McGwin G, Vilá L M, Petri M A, Vyse T J, Merrill J T, James J A, Nath S K, Harley J B, Guthridge J M
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Genes Immun. 2009 Jul;10(5):531-8. doi: 10.1038/gene.2009.18. Epub 2009 Apr 2.
Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value=1.97 x 10(-5), odds ratio (OR)=1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value=2.59 x 10(-5), OR=1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.
系统性红斑狼疮（SLE）是一种临床表现高度多变的自身免疫性疾病。患者存在针对T细胞、B细胞及辅助细胞功能的免疫异常。SLE患者的B细胞处于过度活跃状态。在先前一项研究中报告称，一种在B细胞中表达的衔接蛋白BANK1（含锚蛋白重复序列的B细胞支架蛋白）在欧洲人群中与SLE相关。本研究的目的是在一个独立的重复样本中评估BANK1基因分型与表型的关联。我们对1892例欧洲裔SLE患者和2652例欧洲裔对照的BANK1基因中的38个单核苷酸多态性（SNP）进行了基因分型。与SLE和BANK1关联最强的是rs17266594（校正P值 = 1.97×10⁻⁵，比值比（OR） = 1.22，95%置信区间1.12 - 1.34）和rs10516487（校正P值 = 2.59×10⁻⁵，OR = 1.22，95%置信区间1.11 - 1.34）。我们的研究结果表明，这种关联由这两个SNP解释，证实了先前的报道，即这些多态性会增加患狼疮的风险。对富集了血液学、免疫学和肾脏ACR标准或自身抗体水平（如抗RNP A和抗SmRNP）的患者亚组进行分析，发现了BANK1的其他关联。我们的结果表明，BANK1多态性会改变免疫系统的发育和功能，从而增加患狼疮的风险。
