Fine mapping of a region of chromosome 11q23.3 reveals independent locus associated with risk of glioma

PLoS One. 2012;7(12):e52864. doi: 10.1371/journal.pone.0052864. Epub 2012 Dec 31.

Abstract

Background: A single nucleotide polymorphism (SNP) at locus 11q23.3 (rs498872) in the near 5'-UTR of the PHLDB1 gene was recently implicated as a risk factor for gliomas in a genome-wide association study, and this involvement was confirmed in three additional studies.

Methodology/principal findings: To identify possible causal variants in the region, the authors genotyped 15 tagging SNPs in the 200 kb genomic region at 11q23.3 locus in a Chinese Han population-based case-control study with 983 cases and 1024 controls. We found evidence for an association between two independent loci (both the PHLDB1 and the ACRN1 genes) and a predisposition for gliomas. Among the multiple significant SNPs in the PHLDB1 gene region, the rs17749 SNP was the most significant [P = 1.31×10⁻⁶ in a recessive genetic model]. Additionally, two novel SNPs (rs2236661 and rs494560) that were independent of rs17749 were significantly associated with glioma risk in a recessive genetic model [P = 1.31×10⁻⁵ and P = 3.32×10⁻⁵, respectively]. The second novel locus was within the ARCN1 gene, and it was associated with a significantly reduced risk for glioma.

Conclusions/significance: Our data strongly support PHLDB1 as a susceptibility gene for glioma, also shedding light on a new potentially candidate gene, ARCN1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics*
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11 / genetics*
  • Coatomer Protein / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glioma / genetics*
  • Haplotypes
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Linkage Disequilibrium
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sequence Analysis, DNA

Substances

  • Coatomer Protein
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • PHLDB1 protein, human

Grants and funding

This work was partially supported by Shanghai Science and Technology Research Program (09JC1402200), Natural Science Foundation of China (81001114), the Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry) and the Doctoral Fund of Ministry of Education of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.