LncRNA GAS5 Indel Genetic Polymorphism Contributes to Glioma Risk Through Interfering Binding of Transcriptional Factor TFAP2A.

Abstract

Long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) accumulates in growth-arrested cells and plays a crucial role in progression of multiple cancers, including glioma. There is a functional GAS5 rs145204276 indel genetic polymorphism in the promoter region. However, it is still largely unknown how the GAS5 indel genetic polymorphism is involved in etiology of glioma. We evaluated the association between the GAS5 indel genetic polymorphism and glioma development in a Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression adjusted by age and sex. We found that carriers of the GAS5 del allele was significantly associated with elevated risk of glioma (OR = 1.71, 95% CI = 1.34-2.18, p = 1.7 × 10-5). Compared with the GAS5 ins/ins genotype, the ins/del genotype or the del/del genotype was significantly associated with 1.57-fold or 2.61-fold increased glioma susceptibility (p = 0.001 or p = 9.0 × 10-6). When patients were stratified by disease subtypes, The GAS5 indel polymorphism was not significantly associated with risk of oligodendroglial tumor (p = 0.353). Integrated analyses indicated that the GAS5 indel polymorphism might alert the binding of transcriptional factor TFAP2A and activation of its expression based on ENCODE and REMBRANDT databases. Our results highlight the importance and potential of the biological relevance of the GAS5 indel genetic variant in glioma predisposition.

• Authors: Jupeng Yuan, Nasha Zhang, Yan Zheng, Yi-Dong Chen, Jie Liu, Ming Yang
• Journal: DNA and cell biology (DNA Cell Biol) Vol. 37 Issue 9 Pg. 750-757 (Sep 2018) ISSN: 1557-7430 [Electronic] United States
• PMID: 30074406 (Publication Type: Journal Article)

Chemical References

• GAS5 long non-coding RNA, human
• RNA, Long Noncoding
• TFAP2A protein, human
• Transcription Factor AP-2

Topics

• Adult
• Case-Control Studies
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Glioma (genetics)
• Humans
• INDEL Mutation
• Male
• Polymorphism, Genetic
• Prognosis
• Promoter Regions, Genetic
• Protein Binding
• RNA, Long Noncoding (genetics)
• Transcription Factor AP-2 (genetics, metabolism)