A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-α levels

Steffan D. Bos, Nico Lakenberg, Ruud Van Der Breggen, Jeanine J. Houwing-Duistermaat, Margreet Kloppenburg, Anton Jm De Craen, Marian Beekman, Ingrid Meulenbelt, P. Eline Slagboom

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Cytokines are major immune system regulators. Previously, innate cytokine profiles determined by lipopolysaccharide stimulation were shown to be highly heritable. To identify regulating genes in innate immunity, we analyzed data from a genome-wide linkage scan using microsatellites in osteoarthritis (OA) patients (The GARP study) and their innate cytokine data on interleukin (IL)-1Β, IL-1Ra, IL-10 and tumor necrosis factor (TNF)α. A confirmation cohort consisted of the Leiden 85-Plus study. In this study, a linkage analysis was followed by manual selection of candidate genes in linkage regions showing LOD scores over 2.5. An single-nucleotide polymorphism (SNP) gene tagging method was applied to select SNPs on the basis of the highest level of gene tagging and possible functional effects. QTDT was used to identify the SNPs associated with innate cytokine production. Initial association signals were modeled by a linear mixed model. Through these analyses, we identified 10 putative genes involved in the regulation of TNFα. SNP rs6679497 in gene CD53 showed significant association with TNFα levels (P0.001). No association of this SNP was observed with OA. A novel gene involved in the innate immune response of TNFα is identified. Genetic variation in this gene may have a role in diseases and disorders in which TNFα is closely involved.

Original languageEnglish
Pages (from-to)953-959
Number of pages7
JournalEuropean Journal of Human Genetics
Volume18
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • CD53
  • GARP
  • TNF
  • immunity
  • linkage
  • osteoarthritis

Fingerprint

Dive into the research topics of 'A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-α levels'. Together they form a unique fingerprint.

Cite this