Over one-third of African-American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg-7, an autosomal dominantly inherited risk factor for MGUS/MM.
As hyperphosphorylated paratarg-7 (pP-7) carrier state was shown to be the first molecularly defined autosomal dominantly inherited risk factor for monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European population, the prevalence of pP-7 carrier state among African-Americans who have a significantly higher incidence of MGUS/MM is of interest. We therefore determined pP-7 carrier state and paraproteins with specificity for P-7 in African-American, European and Japanese patients with MGUS/MM and healthy controls. By isoelectric focusing and ELISA, a paratarg-7-specific paraprotein and the associated pP-7 carrier state was observed in 30/81 (37.0%) African-American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients (p < 0.001). A pP-7 carrier state was found in 11/100 (11.0%) African-American, 8/550 (1.5%) European and 1/278 (0.4%) Japanese healthy controls (p < 0.001), resulting in an odds ratio for MGUS/MM of 4.8 (p < 0.001) among African-American, 13.6 among European (p < 0.001) and 11.5 (p = 0.023) among Japanese carriers of pP-7. We conclude that pP-7 carriers are most prevalent among African-Americans, but a pP-7 carrier state is the strongest molecularly defined single risk factor for MGUS/MM known to date in all three ethnic groups. The high prevalence of pP-7 carriers among African-American patients emphasizes a predominant role of this genetic factor in the pathogenesis of these diseases. The large number of pP7 African-American patients and controls should facilitate the identification of the SNP or mutation underlying the pP-7 carrier state.
Department of Internal Medicine I, José-Carreras-Center for Immuno and Gene Therapy, Homburg/Saar, Germany.
Carsten
C
Zwick
Gerhard
G
Held
Michaela
M
Auth
Leon
L
Bernal-Mizrachi
John D
JD
Roback
Susan
S
Sunay
Shinsuke
S
Iida
Yoshiaki
Y
Kuroda
Akira
A
Sakai
Marita
M
Ziepert
Ryuzo
R
Ueda
Michael
M
Pfreundschuh
Klaus-Dieter
KD
Preuss
D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005060:Europe; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D007525:Isoelectric Focusing; D007564:Japan; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000208:ethnology* / Q000235:genetics*; D009101:Multiple Myeloma / Q000208:ethnology* / Q000235:genetics*; D009154:Mutation; D016017:Odds Ratio; D010266:Paraproteins / Q000235:genetics*; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D054648:Protein Phosphatase 2 / Q000235:genetics*; D012307:Risk Factors; D014481:United States
D010266:Paraproteins; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2
MGUS; genetics; multiple myeloma; risk factors