Department of General Surgery, Changzhou No. 3 People's Hospital, Changzhou, Jiangsu Province, China.
Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20194229.
C677T (Ala>Val, rs1801133 C>T), a non-synonymous variant of methylenetetrahydrofolate reductase (MTHFR) gene, has been found to be associated with an impair enzyme activity of MTHFR. The relationship of MTHFR rs1801133 with hepatocellular carcinoma (HCC) has been extensively investigated. However, the findings were conflicting. Recently, more investigations have been conducted on the relationship of MTHFR rs1801133 with HCC. To obtain a more precise assessment on the effect of this non-synonymous variant to the development of HCC, a pooled-analysis was performed. This meta-analysis consisted of 19 independent case-control studies. By using the odds ratio (OR) combined with 95% confidence interval (CI), the relationship of MTHFR rs1801133 with HCC risk was determined. A total of 19 independent case-control studies were included. Finally, 6,102 HCC cases and 6,526 controls were recruited to examine the relationship of MTHFR rs1801133 with HCC risk. In recessive model (TT vs. CC/CT), the findings reached statistical significance (OR, 0.90; 95%CI, 0.82-0.98; P = 0.016). Subgroup analysis also found an association between MTHFR rs1801133 polymorphism and the decreased risk of HCC in hepatitis/virus related patients (recessive model: OR, 0.85; 95%CI, 0.72-0.99; P = 0.035, and allele model: OR, 0.90; 95%CI, 0.81-0.99; P = 0.028). Subgroup analyses indicated that extreme heterogeneity existed in Asian population, larger sample size investigation, hospital-based study and normal/healthy control subgroups. The shape of Begger's seemed symmetrical. Egger's linear regression test also confirmed these evaluations. Sensitivity analyses suggested that our findings were stable. In summary, our results highlight that MTHFR rs1801133 polymorphism decreases HCC susceptibility. The relationship warrants a further assessment.
C677T（Ala>Val，rs1801133 C>T）是亚甲基四氢叶酸还原酶（MTHFR）基因的一种非同义突变，已被发现与 MTHFR 酶活性受损有关。MTHFR rs1801133 与肝细胞癌（HCC）的关系已被广泛研究。然而，研究结果存在矛盾。最近，更多的研究已经针对 MTHFR rs1801133 与 HCC 的关系进行了研究。为了更准确地评估这种非同义突变对 HCC 发展的影响，进行了荟萃分析。这项荟萃分析包括 19 项独立的病例对照研究。通过使用优势比（OR）结合 95%置信区间（CI），确定了 MTHFR rs1801133 与 HCC 风险的关系。共纳入 19 项独立的病例对照研究。最后，共招募了 6102 例 HCC 病例和 6526 例对照，以检验 MTHFR rs1801133 与 HCC 风险的关系。在隐性模型（TT 与 CC/CT）中，结果具有统计学意义（OR，0.90；95%CI，0.82-0.98；P=0.016）。亚组分析还发现，MTHFR rs1801133 多态性与肝炎/病毒相关患者 HCC 风险降低之间存在关联（隐性模型：OR，0.85；95%CI，0.72-0.99；P=0.035，等位基因模型：OR，0.90；95%CI，0.81-0.99；P=0.028）。亚组分析表明，亚洲人群存在明显的异质性，样本量较大的研究、医院为基础的研究和正常/健康对照组。贝格的形状似乎是对称的。埃格的线性回归检验也证实了这些评估。敏感性分析表明，我们的研究结果是稳定的。总之，我们的研究结果强调，MTHFR rs1801133 多态性降低 HCC 的易感性。这一关系需要进一步评估。
