Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.
| العنوان: | Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma. |
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| المؤلفون: | Swaminathan, Bhairavi, Thorleifsson, Guðmar, Jöud, Magnus, Ali, Mina, Johnsson, Ellinor, Ajore, Ram, Sulem, Patrick, Halvarsson, Britt-Marie, Eyjolfsson, Guðmundur, Haraldsdottir, Vilhelmina, Hultman, Christina, Ingelsson, Erik, Kristinsson, Sigurður Y, Kähler, Anna K, Lenhoff, Stig, Masson, Gisli, Mellqvist, Ulf-Henrik, Månsson, Robert, Nelander, Sven, Olafsson, Isleifur, Sigurðardottir, Olof, Steingrimsdóttir, Hlif, Vangsted, Annette, Vogel, Ulla, Waage, Anders, Nahi, Hareth, Gudbjartsson, Daniel F, Rafnar, Thorunn, Turesson, Ingemar, Gullberg, Urban, Stefánsson, Kári, Hansson, Markus, Thorsteinsdóttir, Unnur, Nilsson, Björn |
| المصدر: | Nature Communications BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation. 6:1-8 |
| مصطلحات موضوعية: | Medicin och hälsovetenskap, Klinisk medicin, Hematologi, Medical and Health Sciences, Clinical Medicine, Hematology |
| الوصف: | 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). |
| وصف الملف: | electronic |
| URL الوصول: | https://lup.lub.lu.se/record/5442375 https://portal.research.lu.se/files/3058416/8523062 http://www.ncbi.nlm.nih.gov/pubmed/26007630?dopt=Abstract http://dx.doi.org/10.1038/ncomms8213 |
| قاعدة البيانات: | SwePub |
| تدمد: | 20411723 |
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| DOI: | 10.1038/ncomms8213 |