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Response to cyclophosphamide may have genetic link for patients with lupus nephritis
The FCGR2B-FCRLA locus was associated with response to treatment with cyclophosphamide by patients with lupus nephritis, according to results of a study in which investigators used a genome-wide association approach.
Researchers studied 109 Korean patients recruited from the Hanyang University Hospital for Rheumatic Diseases in Seoul, Korea. Patients had systemic lupus erythematosus and lupus nephritis, with greater than 500 mg/day proteinuria. All patients were treated with IV cyclophosphamide at doses based on either the Euro-Lupus regimen or the NIH regimen.
Renal response was evaluated at 6 months, and patients were categorized into three groups, including complete, partial and non-responders. Genome-wide single-nucleotide polymorphism (SNP) data of the patients was obtained using Illumina Human 610-Quad BeadChip.
Improved renal outcomes were found for 93 of 109 patients after 6 months, including 67 patients who demonstrated a partial response and 26 patients who had a complete response. No clinical or demographic variables were associated with response, including baseline proteinuria levels or total dose of cyclophosphamide.
Genomic analysis showed SNP rs6697139 in human chromosome 1q23, located between FCGR2B and FCRLA, was significantly associated with response to treatment with cyclophosphamide. The non-responder group had its minor allele A, while the responder group did not.
Investigators also found a suggestive association with response at the SNP rs17411858 located between FCGR2B and FCGR3B at around 40 kb upstream of rs6697139, and carriage of the minor allele in SNP rs17411858 was found only in the group of patients who responded to treatment. Three of 11 identified SNPs, which were located next to one another in the intergenic region between FCGR2B and FCRLA, were significantly associated with response to treatment and passed the genome-wide association study significance threshold. – by Shirley Pulawski
Disclosure: The research was supported by the Korea Healthcare Technology R&D Project of the Ministry for Health and Welfare (HI13C2124 to S-CB) and the National Research Foundation of Korea (2014044403).