Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.
Nat Commun
; 6: 7213, 2015 May 26.
Article
en En
| MEDLINE
| ID: mdl-26007630
ABSTRACT
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).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
/
4_TD
Problema de salud:
3_zoonosis
/
4_meningitis
Asunto principal:
Inmunoglobulina A
/
Inmunoglobulina G
/
Proteínas
/
Factores de Elongación Transcripcional
/
Mieloma Múltiple
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Límite:
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suecia