title: Risk of Japanese carriers of hyperphosphorylated paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasms, to develop monoclonal gammopathy of undetermined significance and multiple myeloma.
abstract: Hyperphosphorylated paratarg-7 (pP-7) is a frequent target of paraproteins in German patients with monoclonal gammopathy of undetermined significance (MGUS)/multiple myeloma (MM). The frequency of MGUS/MM is lower in Japan than in Europe. As pP-7, the first molecularly defined autosomal-dominant risk factor for any hematological neoplasm, is inherited in a dominant fashion, we determined the incidence of the pP-7 carrier state in a Japanese population, and compared the frequency of pP-7-specific paraproteins and the pP-7 carrier state in Japanese and German patients with MGUS/MM. Peripheral blood from 111 Japanese patients with MGUS/MM and 278 healthy blood donors was analyzed for the pP-7 carrier state by isoelectric focusing and for pP-7-specific antibodies by ELISA. The Japanese group was compared with 252 German MGUS/MM patients and 200 healthy controls. Five of 111 (4.5%) Japanese and 35/252 (13.9%) German IgA/IgG MGUS/MM patients had a pP-7-specific paraprotein (P=0.009). The prevalence of healthy pP-7 carriers in the Japanese study group was 1/278 (0.36%), whereas it was 4/200 in the German group (P=0.166). The relative risk for pP-7 carriers developing MGUS/MM had an odds ratio of 13.1 in the Japanese and 7.9 in the German group. In conclusion, the fraction of pP-7 carriers with a pP-7-specific paraprotein is lower among Japanese than in German patients with MGUS/MM, but pP-7 carriers in both ethnic groups have a high risk of developing MGUS/MM.
authors.affiliation: Jóse-Carreras-Center for Immuno and Gene Therapy, Department of Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Grass
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wikowicz
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inagaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimizu
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
mesh_terms: D044466:Asian People; D001798:Blood Proteins / Q000032:analysis / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005799:Genes, Dominant; D005858:Germany; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000209:etiology / Q000235:genetics*; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics*; D010266:Paraproteins / Q000502:physiology*; D010766:Phosphorylation; D012307:Risk Factors
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D010266:Paraproteins; C406287:STOML2 protein, human