Background Lupus Nephritis (LN) is a cause of significant morbidity in SLE. While the genetic background to SLE has been well characterized, less is known about genes predisposing to LN.
Methods The study consisted of 2886 SLE patients, including 947 (33%) with LN. The discovery cohort (Sweden, n=1091) and replication cohort 1 (US, n=962) were genotyped on the Immunochip and replication cohort 2 (Norway/Denmark, n=833) on a custom array chip. Allele frequencies were compared between patients with LN and LN-negative patients. SNPs with a p-value <0.001 in the LN vs LN-negative analysis in the discovery cohort (nSNPs=139) were analyzed in replication cohort 1. Ten SNPs associated to LN (p<0.0002) in the discovery cohort were genotyped in replication cohort 2. A Bonferroni-corrected p-value of <1.0×10-6 correcting for 48,000 independent SNPs was considered significant.
Results In the discovery cohort, strong association to LN was found with several highly linked SNPs in BANK1, with the top signal in the intronic SNP rs4699261 (p=9.9×10-5, OR 0.66). The association was also present in replication cohort 1 (p=9.5×10-4). In a meta-analysis of the discovery and replication cohort 1, a total of 20 SNPs in BANK1 were associated to LN with the highest signal in rs4699261 (p=3.3×10-7). There was a tendency towards association in replication cohort 2 (p=0.05) and in a meta-analysis of all cohorts, the association with BANK1 was strengthened (p=1.7×10-7).
Conclusion BANK1 variations are associated with LN in patients with SLE. Upregulated BANK1 expression in renal biopsies from LN patients has previously been shown, however the exact role of BANK1 in LN pathogenesis remains to be elucidated.
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