Using a Fishers exact test, we observed a significant protective effect of the minor A allele on the risk of SLE. theBANK1locus with the disease in the two ethnicities separately. Using a Fishers exact test, the minor allele frequency (MAF) of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR) of 0.64 (95% CI 0.49-0.85; one-sided p = 7.07 104). Furthermore, the MAF of rs10516487 in the AA cases was 18.7% while it was 23.3% in AA controls, yielding a protective OR of 0.75 (95% CI 0.551.034; one-sided p = 0.039). The OR of theBANK1variant in our study cohorts is highly comparable with that reported previously in a South American/European SLE case-control cohort (OR = 0.72). As such, R61H in theBANK1gene confers a similar magnitude of SLE protection, not only in European Americans, but also in African Americans. Keywords:systemic lupus erythematosus, African Americans, European Americans,BANK1gene == Introduction == Systemic lupus erythematosus (SLE) is a multi-system, autoimmune inflammatory disease with complex genetic inheritance, characterized by the production of autoantibodies and complement-mediated tissue destruction.15 SLE primarily impacts women (~9:1 ratio), particularly during child-bearing years, with an estimated prevalence of 31 per 100,000 in populations of European ancestry.6,7This disorder has a strong genetic component,79with the estimated concordance rate among monozygotic twins (~30%) being approximately ten times the rate among dizygotic twins (~3%), which is line with a high sibling relative risk ratio (s= 29).7,8 During the past 20 years, many linkage and candidate gene studies have been carried out in order to identify genetic variants contributing to the pathogenesis to SLE. Replicated linkages with SLE have been reported at multiple loci. For example, haplotypes carrying the HLA class II allelesDRB1*0301andDRB1*1501are LEFTY2 strongly established as being associated with SLE.1012Replicated associations with SLE and variants in candidate genes include the HLA region,12FCGR3A,13,14FCGR2A,15PDCD1,16andPTPN22.17More recently, variants of the genes encoding interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) have been shown to be risk factors for SLE.1821 Recently, a number of genome wide association studies have reported remarkably strong, replicable signals with complex disease, including theKIAA0350gene in PF-2341066 (Crizotinib) type 1 diabetes22andIL23Rin inflammatory bowel disease.23In January 2008, through the utilization of the Illumina HumanHap300 BeadChip, Kozyrev et al24added to this repertoire by reporting a highly significant association between SLE and theBANK1gene [NM_017935] on chromosome 4q24, which encodes a B-cell adaptor protein. Specifically, an common coding variant, rs10516487 (R61H), was shown to confer a strong protective effect against the disease and was then replicated in the same study in separate South American and European cohorts of patients with SLE. The authors hypothesized that this variant could contribute to sustained B cellreceptor signaling and B-cell hyperactivity, a key feature of this disease. Although theseBANK1findings are compelling, there are PF-2341066 (Crizotinib) continuing concerns regarding the performance of association studies in complex traits; as such independent replication efforts are now considered mandatory. 25With the many errors and biases that can blight any individual study, replication by others can ensure that the original findings are robust and can also provide a more accurate estimate of the likely effect size.26,27 In this study we demonstrate that the variant, rs10516487, in theBANK1gene confers a similar magnitude of protection of SLE as reported previously, not only in European Americans, but also in African Americans further suggesting PF-2341066 (Crizotinib) that the B-cell pathway may be causally linked to SLE. == Results == == Association between rs10516487 and SLE risk in Caucasians == In this replication attempt, we genotyped 178 SLE cases and 1808 population-based controls (all European Americans) with the Illumina HumanHap550 Genotyping BeadChip as part of our ongoing genome-wide association study of the disease. The diagnosis of SLE was based on standard criteria (see Study Subjects section). The.