Viral Genetic Engineering Laboratory, Romanian Academy Stefan S. Nicolau Virology Institute, Bucharest 030304, Romania.
J Cell Mol Med. 2013 Apr;17(4):543-9. doi: 10.1111/jcmm.12032. Epub 2013 Feb 28.
The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV.
本研究旨在探讨亚甲基四氢叶酸还原酶（MTHFR）多态性和 MTHFR 甲基化模式在罗马尼亚女性宫颈癌病变发展中的作用，罗马尼亚是一个人乳头瘤病毒（HPV）宫颈感染流行率较高的国家。为了实现这一目标，我们对 77 名女性的血液样本和宫颈细胞学标本（n=77）/肿瘤组织标本（n=23）以及 50 名对照者的血液和阴性细胞学涂片进行了研究。研究发现，C677T 多态性的 T 等位基因与宫颈病变之间存在显著关联，杂合子女性发生宫颈癌的风险增加了三倍（正常/宫颈病变和肿瘤：野生纯合子 34/41（0.68/0.41），杂合子 14/51（0.28/0.51），突变纯合子 2/8（0.04/0.08）；OR=3.081，P=0.0035）。在对照组中使用 χ 平方检验，HPV 阴性和 HPV 阳性的宫颈病变患者中，病毒感染与 C677T 多态性的 T 等位基因之间存在显著相关性（P=0.0287）。所有 HGSIL 和肿瘤样本的 MTHFR 启动子均发生甲基化，HPV 阳性样本、对照组和无 HPV DNA 的宫颈发育不良病变病例之间存在显著差异（P<0.0001），高危（hr）HPV 与低危（lr）HPV 患者样本之间也存在显著差异（P=0.0026）。多态性与甲基化之间无相关性。在罗马尼亚，携带 T 等位基因的个体易患宫颈病变。MTHFR 启动子甲基化与宫颈病变的严重程度以及与高危型 HPV 有关。
