Department of Nutrition Science, Friedman School of Nutrition Science, Tufts University, Boston, MA, USA.
Epigenetics. 2011 May;6(5):623-9. doi: 10.4161/epi.6.5.15335.
Reduced levels of global DNA methylation are associated with genomic instability and are independent predictors of cancer risk. Little is known about the environmental determinants of global DNA methylation in peripheral blood. We examined the association between demographic and lifestyle factors and levels of global leukocyte DNA methylation in 161 cancer-free subjects enrolled in the North Texas Healthy Heart Study aged 45-75 years in 2008. We used in-person interviews for demographics and lifestyle factors, a self-administrated Block food frequency questionnaire for diet, and bioelectrical impedance analysis and CT-scan for body composition. We measured genomic DNA methylation using bisulfite conversion of DNA and pyrosequencing for LINE-1. Body composition measures including body mass index, waist circumference, areas of subcutaneous fat and visceral fat, percent of fat mass and fat-free mass were not associated with global genomic DNA methylation after controlling the effect of age, gender and race/ethnicity. Instead, female gender was significantly associated with a reduced level of global methylation (β = -2.77, 95% CI: -4.33, -1.22). Compared to non-Hispanic whites, non-Hispanic blacks (β = -2.02, 95% CI: -3.55, -0.50) had significantly lower levels of global methylation. No association was found with age, cigarette smoking, alcohol drinking and dietary intake of nutrients in one-carbon metabolism. Global leukocyte DNA methylation differs by gender and race/ethnicity, suggesting these variables need to be taken into consideration in studies of global DNA methylation as an epigenetic marker for cancer.
全球 DNA 甲基化水平降低与基因组不稳定性有关，是癌症风险的独立预测因子。外周血中全球 DNA 甲基化的环境决定因素知之甚少。我们研究了人口统计学和生活方式因素与 161 名无癌症的北德克萨斯健康心脏研究参与者的白细胞全基因组 DNA 甲基化水平之间的关系，这些参与者年龄在 45-75 岁之间，于 2008 年入组。我们通过面对面访谈获取人口统计学和生活方式因素，使用自我管理的 Block 食物频率问卷获取饮食信息，以及生物电阻抗分析和 CT 扫描获取身体成分信息。我们使用亚硫酸氢盐转化 DNA 和焦磷酸测序来测量 LINE-1 中的基因组 DNA 甲基化。在控制年龄、性别和种族/民族的影响后，身体成分测量值（包括体重指数、腰围、皮下脂肪和内脏脂肪面积、体脂肪百分比和去脂体重）与全基因组 DNA 甲基化无关。相反，女性性别与全甲基化水平降低显著相关（β=-2.77，95%CI：-4.33，-1.22）。与非西班牙裔白人相比，非西班牙裔黑人（β=-2.02，95%CI：-3.55，-0.50）的全基因组甲基化水平显著降低。年龄、吸烟、饮酒以及一碳代谢营养素的饮食摄入量与全白细胞 DNA 甲基化无相关性。白细胞全基因组 DNA 甲基化存在性别和种族/民族差异，这表明在以全基因组 DNA 甲基化为癌症表观遗传标志物的研究中，需要考虑这些变量。
