title: Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the FCGR2B-FCRLA Locus.
abstract: 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.
  
  
  
  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.
  
  
  
  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 (r(2) = 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%).
  
  
  
  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.
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Bang
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Joo
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases.
authors.forename: Taehyeung
authors.initials: T
authors.lastname: Kim
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases.
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases. ckang@kaist.ac.kr scbae@hanyang.ac.kr.
authors.forename: Changwon
authors.initials: C
authors.lastname: Kang
authors.affiliation: From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon; and the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.K. Kim*, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, and Hanyang University Hospital for Rheumatic Diseases; S.Y. Bang*, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; Y.B. Joo, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; T. Kim, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; H.S. Lee, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases; C. Kang, PhD, Department of Biological Sciences, Korea Advanced Institute of Science and Technology; S.C. Bae, MD, PhD, MPH, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases. ckang@kaist.ac.kr scbae@hanyang.ac.kr.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000483:Alleles; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011961:Receptors, Fc; D017452:Receptors, IgG / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C499173:FCGR2B protein, human; C452186:FCRLA protein, human; D007166:Immunosuppressive Agents; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D003520:Cyclophosphamide
keywords: CYCLOPHOSPHAMIDE; GENETIC STUDIES; LUPUS NEPHRITIS