A lower degree of PBMC L1 methylation is associated with excess body weight and higher HOMA-IR in the presence of lower concentrations of plasma folate.

A lower degree of PBMC L1 methylation is associated with excess body weight and higher HOMA-IR in the presence of lower concentrations of plasma folate.
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DOI:
10.1371/journal.pone.0054544
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Johanning GL
Johanning GL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Piyathilake CJ;Badiga S;Alvarez RD;Partridge EE;Johanning GL

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确定全球DNA甲基化与超重(EBW)和相关疾病及其修饰因子之间的关联是一项尚未满足的研究需求,可能会导致人类DNA甲基化相关疾病风险的降低。本研究的目的是评估以下内容:1)外周血单核细胞(PBMC)L1甲基化程度与叶酸和EBW指标之间的相关性,2)PBMC L1甲基化程度与叶酸和胰岛素抵抗(IR)之间的相关性,如较高稳态模型评估(HOMA-IR)所示。研究人群包括470名被诊断为pap异常的育龄妇女。通过焦磷酸测序评估PBMC L1甲基化的程度。Logistic回归模型将EBW指标(体重指数-BMI、体脂-BF和腰围-WC)或HOMA-IR作为因变量,将PBMC L1甲基化程度和循环叶酸浓度作为主要关注的独立预测因子。PBMC L1甲基化程度较低和血浆叶酸浓度较低的女性更可能具有较高的BMI、% BF或WC(分别为OR = 2.49,95% CI:1.41-4.47,P = 0.002; OR = 2.49,95% CI:1.40-4.51,P = 0.002和OR = 1.98,95%CI:1.14-3.48,P = 0.0145)和较高的HOMA-IR(OR = 1.78,95% CI:1.02-3.13,P = 0.041)。                  我们的研究结果表明,较低程度的PBMC L1甲基化与超重和较高的HOMA-IR相关,特别是在血浆叶酸浓度较低的情况下。
Identification of associations between global DNA methylation and excess body weight (EBW) and related diseases and their modifying factors are an unmet research need that may lead to decreasing DNA methylation-associated disease risks in humans. The purpose of the current study was to evaluate the following; 1) Association between the degree of peripheral blood mononuclear cell (PBMC) L1 methylation and folate, and indicators of EBW, 2) Association between the degree of PBMC L1 methylation and folate, and insulin resistance (IR) as indicated by a higher homeostasis model assessment (HOMA-IR). The study population consisted of 470 child-bearing age women diagnosed with abnormal pap. The degree of PBMC L1 methylation was assessed by pyrosequencing. Logistic regression models specified indicators of EBW (body mass index–BMI, body fat–BF and waist circumference–WC) or HOMA-IR as dependent variables and the degree of PBMC L1 methylation and circulating concentrations of folate as the independent predictor of primary interest. Women with a lower degree of PBMC L1 methylation and lower plasma folate concentrations were significantly more likely to have higher BMI, % BF or WC (OR = 2.49, 95% CI:1.41–4.47, P = 0.002; OR = 2.49, 95% CI:1.40–4.51, P = 0.002 and OR = 1.98, 95%  = 1.14–3.48 P = 0.0145, respectively) and higher HOMA-IR (OR = 1.78, 95% CI:1.02–3.13, P = 0.041). Our results demonstrated that a lower degree of PBMC L1 methylation is associated with excess body weight and higher HOMA-IR, especially in the presence of lower concentrations of plasma folate.
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