Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the FCGR2B-FCRLA Locus

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Objective. Cyclophosphamide (CYC) is an immunosuppressant drug widely used to treat various diseases including lupus nephritis, but its efficacy highly varies from individual to individual. This pharmacogenomics association study searched for genetic variations associated with CYC efficacy. Methods. Genome-wide association scan was performed for 109 Korean patients with systemic lupus erythematosus with lupus nephritis (classes III-V) who received intravenous CYC induction therapy. Genetic differences between responders and nonresponders were examined using Cochran-Armitage trend tests, and genotype imputation was used for defining the association locus. Results. Genetic polymorphisms in the Fc gamma receptor gene (FCGR) cluster at human chromosome 1q23, previously associated with lupus nephritis susceptibility, were associated with the response to CYC treatment for lupus nephritis. Significant response association was found for 3 perfectly correlated (r(2) = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 x 10(-8)). Carriage of the minor alleles in these SNP was found only in nonresponders (31%) and none in responders (0%). Conclusion. This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy.
Publisher
J RHEUMATOL PUBL CO
Issue Date
2016-06
Language
English
Article Type
Article
Keywords

PULSE CYCLOPHOSPHAMIDE; COPY NUMBER; THERAPY; ERYTHEMATOSUS; MANAGEMENT; RECEPTORS

Citation

JOURNAL OF RHEUMATOLOGY, v.43, no.6, pp.1045 - 1049

ISSN
0315-162X
DOI
10.3899/jrheum.150665
URI
http://hdl.handle.net/10203/213648
Appears in Collection
BS-Journal Papers(저널논문)
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