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Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma
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2015 (English)In: Nature Communications, ISSN 2041-1723, Vol. 6, 7213Article in journal (Refereed) Published
Abstract [en]

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 x 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 x 10(-9) and P = 6.4 x 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR = 1.30; P = 0.0024).

Place, publisher, year, edition, pages
2015. Vol. 6, 7213
National Category
Immunology in the medical area
URN: urn:nbn:se:uu:diva-257040DOI: 10.1038/ncomms8213ISI: 000355537600004PubMedID: 26007630OAI: diva2:828104
Available from: 2015-06-29 Created: 2015-06-29 Last updated: 2016-01-25Bibliographically approved

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