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Whole exome-wide association study identifies a missense variant in SLC2A4RG associated with glioblastoma risk.
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.
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