TY - JOUR
T1 - Whole exome-wide association study identifies a missense variant in SLC2A4RG associated with glioblastoma risk
AU - Zhao, Yingjie
AU - Yun, Dapeng
AU - Zou, Xiang
AU - Jiang, Tao
AU - Li, Gang
AU - Hu, Lingna
AU - Chen, Juxiang
AU - Xu, Jianfeng
AU - Mao, Ying
AU - Chen, Hongyan
AU - Lu, Daru
N1 - Funding Information:
We would like to thank all participates recruited in this study. This study was supported by the National Natural Science Funds of China (81372706, 81372235 and 81071739).
PY - 2017
Y1 - 2017
N2 - In this study, we conducted a genome-wide scan of single nucleotide polymorphisms (SNPs) to identify coding variants that is associated with the risk of glioblastoma (GBM), the most common and most malignant subtype of glioma. We genotyped 1038 GBM cases and 1008 controls in a Chinese Han population using Illumina HumanExome Beadchip v1.0. A missense variant, rs8957 (E[GAG]233D[GAU], SLC2A4RG, 20q13.33), was found being associated with GBM risk, with an odd ratio (OR) of 1.43 (95% confidence interval (CI) = 1.25-1.64, P = 1.72E- 07). The G > T transversion at rs8957 leading to changes of subcellular localization of SLC2A4RG, possibly due to the impairment of its nuclear export signal or protein folding. Moreover, the amino acid substitution compromised the function of SLC2A4RG as a cancer suppressor by promoting cell growth through de-inhibition of CDK1 in U87 and U251 cell lines. These results suggest SLC2A4RG plays an important role in the etiology of GBM and may be a potential therapeutic target.
AB - In this study, we conducted a genome-wide scan of single nucleotide polymorphisms (SNPs) to identify coding variants that is associated with the risk of glioblastoma (GBM), the most common and most malignant subtype of glioma. We genotyped 1038 GBM cases and 1008 controls in a Chinese Han population using Illumina HumanExome Beadchip v1.0. A missense variant, rs8957 (E[GAG]233D[GAU], SLC2A4RG, 20q13.33), was found being associated with GBM risk, with an odd ratio (OR) of 1.43 (95% confidence interval (CI) = 1.25-1.64, P = 1.72E- 07). The G > T transversion at rs8957 leading to changes of subcellular localization of SLC2A4RG, possibly due to the impairment of its nuclear export signal or protein folding. Moreover, the amino acid substitution compromised the function of SLC2A4RG as a cancer suppressor by promoting cell growth through de-inhibition of CDK1 in U87 and U251 cell lines. These results suggest SLC2A4RG plays an important role in the etiology of GBM and may be a potential therapeutic target.
KW - Coding variants
KW - Cyclin dependent kinase 1 (CDK1)
KW - Glioblastoma (GBM)
KW - Rs8957 (E[GAG]233D[GAU])
KW - SLC2A4RG
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M3 - Article
AN - SCOPUS:85030635303
SN - 2156-6976
VL - 7
SP - 1937
EP - 1947
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
IS - 9
ER -