外周血单个核细胞中更高程度的 LINE-1 甲基化，一种与一碳营养素相关的表观遗传改变，与发生宫颈上皮内瘤变的风险较低相关。
A higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia.
机构信息
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
出版信息
Nutrition. 2011 May;27(5):513-9. doi: 10.1016/j.nut.2010.08.018.
OBJECTIVE
The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN ≥ 2).
METHODS
This study included 376 women who tested positive for high-risk human papillomaviruses and were diagnosed with CIN ≥ 2 (cases) or CIN ≤ 1 (non-cases). CIN ≥ 2 (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥ 70% versus <70%) and CC LINE-1 methylation (≥ 54% versus <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.
RESULTS
Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN ≥ 2 (odds ratio 0.44, 95% confidence interval 0.24-0.83, P = 0.011), whereas there was no significant association between degree of CC LINE-1 methylation and CIN ≥ 2 (odds ratio 0.86, 95% confidence interval 0.51-1.46, P = 0.578). Among non-cases, women with supraphysiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared with women with lower folate and lower vitamin B12 (odds ratio 3.92, 95% confidence interval 1.06-14.52, P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.
CONCLUSION
These results suggest that a higher degree of LINE-1 methylation in PBMCs, a one-carbon nutrient-related epigenetic alteration, is associated with a lower risk of developing CIN.
目的
本研究旨在评估 LINE-1 甲基化为叶酸和维生素 B12 对发生高级别宫颈上皮内瘤变（CIN≥2）的影响的中间生物标志物。
方法
本研究纳入了 376 名 HPV 高危型阳性且诊断为 CIN≥2（病例）或 CIN≤1（非病例）的女性。CIN≥2（是/否）是逻辑回归模型中的因变量，该模型指定外周血单核细胞（PBMCs）和脱落宫颈细胞（CCs）的 LINE-1 甲基化为主要感兴趣的独立预测因子。在仅针对非病例的分析中，PBMC LINE-1 甲基化（≥70%与<70%）和 CC LINE-1 甲基化（≥54%与<54%）是指定叶酸和维生素 B12 的循环浓度为主要独立预测因子的逻辑回归模型中的因变量。
结果
PBMC LINE-1 甲基化最高三分位的女性患 CIN≥2 的几率降低了 56%（比值比 0.44，95%置信区间 0.24-0.83，P=0.011），而 CC LINE-1 甲基化程度与 CIN≥2 之间没有显著关联（比值比 0.86，95%置信区间 0.51-1.46，P=0.578）。在非病例中，与叶酸浓度较低和维生素 B12 浓度较低的女性相比，叶酸浓度高于生理范围（>19.8ng/mL）和血浆维生素 B12 浓度充足（≥200.6ng/mL）的女性 PBMC 高度甲基化的可能性显著更高（比值比 3.92，95%置信区间 1.06-14.52，P=0.041）。包括叶酸和维生素 B12 在内的任何变量均与 CC LINE-1 甲基化无显著关联。
结论
这些结果表明，PBMC 中更高程度的 LINE-1 甲基化（一种与单碳营养素相关的表观遗传改变）与发生 CIN 的风险降低相关。
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