Fine Mapping of a Region of Chromosome 11q23.3 Reveals Independent Locus Associated with Risk of Glioma |
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| Authors: | Hongyan Chen Bing Sun Yingjie Zhao Xiao Song Weiwei Fan Keke Zhou Liangfu Zhou Ying Mao Daru Lu |
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| Institution: | 1. State Key Laboratory of Genetic Engineering, Fudan-VARI Genetic Epidemiology Center and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.; 2. Neurosurgery Department of Huashan Hospital, Fudan University, Shanghai, China.; McGill University Department of Neurology and Neurosurgery, Canada, |
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| Abstract: | BackgroundA 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 FindingsTo 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/SignificanceOur data strongly support PHLDB1 as a susceptibility gene for glioma, also shedding light on a new potentially candidate gene, ARCN1. |
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