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血管紧张素转换酶插入/缺失(ACE I/D)序列变异而非亚甲基四氢叶酸还原酶(MTHFR)C677T,与恶性胶质瘤风险密切相关,其DD基因型变异可能是胶质瘤患者总生存期的一个有前景的预测生物标志物。

ACE I/D sequence variants but not MTHFR C677T, is strongly linked to malignant glioma risk and its variant DD genotype may act as a promising predictive biomarker for overall survival of glioma patients.

作者信息

Pandith Arshad A, Qasim Iqbal, Zahoor Wani, Shah Parveen, Bhat Abdul R

机构信息

Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, India.

Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, India.

出版信息

Gene. 2018 Jan 10;639:62-68. doi: 10.1016/j.gene.2017.10.013. Epub 2017 Oct 7.

Abstract

OBJECTIVE

ACE I/D and MTHFR C677T gene polymorphisms can be seen as candidate genes for glioma on the basis of their biological functions and their involvement in different cancers. The aim of this study was to analyze potential association and overall survival between MTHFR C677T and ACE I/D polymorphism in glioma patients in our population.

MATERIALS AND METHODS

We tested genotype distribution of 112 glioma patients against 141 cancer-free controls from the same region. Kaplan-Meier survival analysis was performed to evaluate overall survival of patients for both genes.

RESULTS

No significant differences were found among MTHFR C677T wild type C and variant genotypes CT/TT with glioma patients. In ACE, the distribution of variant ID and DD was found to be significantly higher in glioma cases as compared to controls (p<0.0001). ACE DD genotypes were highly presented in glioma cases 26.8% versus 10.6% in controls (p<0.0001) and conferred 5-fold risk for predisposition in glioma cases. Per copy D allele frequency was found higher in cases than in controls (0.54 versus 0.25: p<0.0001). Interestingly we found a significant overall survival (with log rank p<0.01) in patients who presented with ACE DD genotypes had the least estimated overall survival of 13.4months in comparison to 21. 7 and 17.6months for ACE II and I/D genotypes respectively.

CONCLUSION

We conclude ACE I/D polymorphism plays a vital role in predisposition of higher risk for glioma. We also suggest that ACE DD genotypes may act as an important predictive biomarker for overall survival of glioma patients.

摘要

目的

基于ACE I/D和MTHFR C677T基因多态性的生物学功能及其与不同癌症的关联,可将其视为胶质瘤的候选基因。本研究旨在分析我国胶质瘤患者中MTHFR C677T和ACE I/D多态性之间的潜在关联及总生存期。

材料与方法

我们检测了112例胶质瘤患者以及来自同一地区的141例无癌对照的基因型分布。采用Kaplan-Meier生存分析评估这两个基因患者的总生存期。

结果

在胶质瘤患者中,MTHFR C677T野生型C与变异基因型CT/TT之间未发现显著差异。在ACE基因方面,与对照组相比,胶质瘤病例中变异型ID和DD的分布显著更高(p<0.0001)。ACE DD基因型在胶质瘤病例中占比很高,为26.8%,而对照组为10.6%(p<0.0001),且在胶质瘤病例中患癌风险增加5倍。发现病例组中每拷贝D等位基因频率高于对照组(0.54对0.25:p<0.0001)。有趣的是,我们发现携带ACE DD基因型的患者总生存期显著缩短(对数秩检验p<0.01),其估计总生存期最短,为13.4个月,而ACE II和I/D基因型分别为21.7个月和17.6个月。

结论

我们得出结论,ACE I/D多态性在胶质瘤高风险易感性中起重要作用。我们还建议ACE DD基因型可能作为胶质瘤患者总生存期的重要预测生物标志物。

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