TY - JOUR
T1 - Fine Mapping of a Region of Chromosome 11q23.3 Reveals Independent Locus Associated with Risk of Glioma
AU - Chen, Hongyan
AU - Sun, Bing
AU - Zhao, Yingjie
AU - Song, Xiao
AU - Fan, Weiwei
AU - Zhou, Keke
AU - Zhou, Liangfu
AU - Mao, Ying
AU - Lu, Daru
PY - 2012/12/31
Y1 - 2012/12/31
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0052864
DO - 10.1371/journal.pone.0052864
M3 - Article
C2 - 23300798
AN - SCOPUS:84871813019
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 12
M1 - e52864
ER -