Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.
Författare
Summary, in English
Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).
Avdelning/ar
- Hematogenomics
- Myelomgruppen
- Avdelningen för hematologi och transfusionsmedicin
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2015
Språk
Engelska
Sidor
1-8
Publikation/Tidskrift/Serie
Nature Communications
Volym
6
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Hematology
Status
Published
Projekt
- Genetic predisposition for multiple myeloma
Forskningsgrupp
- Hematogenomics
- Myeloma research group
ISBN/ISSN/Övrigt
- ISSN: 2041-1723