TY - JOUR T1 - Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the <em>FCGR2B-FCRLA</em> Locus JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.150665 SP - jrheum.150665 AU - Kwangwoo Kim AU - So-Young Bang AU - Young Bin Joo AU - Taehyeung Kim AU - Hye-Soon Lee AU - Changwon Kang AU - Sang-Cheol Bae Y1 - 2016/03/15 UR - http://www.jrheum.org/content/early/2016/03/09/jrheum.150665.abstract N2 - 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 Fcγ 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 (r2 = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 × 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. ER -