台灣孕婦甲基營養素攝取與印記基因甲基化及類胰島素生長因子相關性

Relationships of Periconceptional Methyl-Donor Nutrients Intake, Germline Genomic and Imprinted Gene Methylation, and Plasma Insulin-Like Growth Factor Levels of Pregnant Women in Taiwan

黃光大(Kuang-Ta Huang) ； 沈育俐(Yu-Li Shen) ； 李建南(Chien-Nan Lee) ； 朱冠宇(Kuan-Yu Chu) ； 王貝文(Bei-Wen Wang) ； 許瑞芬(Rwei-Fen S. Huang)

《台灣營養學會雜誌》 44卷2期 (2020/06) Pp. 52-61

https://doi.org/10.6691/NSJ.202006_44(2).0003

摘要

懷孕期間母親甲基營養素（葉酸／膽鹼／甜菜鹼）的攝取可調節基因體與印記基因DNA的甲基化及生長因子的表達，進而影響胎兒生長發育及重塑子代罹患慢性疾病的風險。目前尚無研究探討台灣孕婦甲基營養素攝取狀況與其基因DNA甲基化的相關性。本研究進行橫斷面人體實驗，由台大婦產科門診及新北市樂寶兒婦幼診所招募116位第一孕期之健康孕婦，經由半定量食物頻率問卷評估甲基營養素攝取狀況；收集血液分析淋巴球基因體甲基化指標LINE-1（long inter-spersed nucleotide element-1）與印記基因H19甲基化標誌，以及被H19調節的類胰島素生長因子（insulin-like growth factor 2）表現。結果顯示，孕婦平均每日總葉酸攝取量1209±877微克，約13.8%孕婦葉酸攝取低於孕期建議攝取參考值。孕婦平均每日總膽鹼攝取量472±306微克，約50%孕婦總膽鹼攝取量低於適當攝取參考值。孕婦葉酸（r = -0.249, p = 0.010）與甜菜鹼（r= -0.252, p = 0.009）攝取量與LINE-1甲基化呈顯著負相關性。多元線性迴歸分析顯示孕婦葉酸，甜菜鹼與總膽鹼攝取量分別預測25%（beta: -0.257, p = 0.008），31%（beta: -0.310, p =0.001）及18% LINE低甲基化（beta: -0.185, p = 0.058）。孕婦甲基營養素攝取量與印記基因H19甲基化以及類胰島素生長因子表現均無顯著相關性。總體而言，台灣孕婦懷孕期間甲基營養素攝取調節母親基因體甲基化程度，而其對胎兒生長發育影響與機轉，有待後續研究。

關鍵字

孕婦 ； 葉酸 ； 膽鹼 ； 甜菜鹼 ； 印記基因 ； DNA甲基化

並列摘要

The intake of periconceptional methyl-donor nutrients (i.e., folate, choline, and betaine) can regulate the methylation of DNA of genes and imprinted genes and expressions of growth factors, which in turn affect fetal growth and remodeling of the risk of chronic diseases. At present, no study has investigated the relationship between methyl nutrient intake and DNA methylation in pregnant women in Taiwan. In this study, a cross-sectional human experiment was performed. In total, 116 healthy pregnant women in the first trimester were recruited from Taiwan National University Hospital and the Loving Care Maternity and Children's Health Centers of New Taipei City, Taiwan. We examined methyl-donor intake with a semiquantitative food frequency questionnaire, and blood was collected to analyze lymphocytic DNA methylation of the H19 imprinted gene and the long interspersed nucleotide element (LINE)-1, as well as plasma insulin-like growth factor (IGF)-2 levels. Results showed that the average methyl-donor intake by the study cohort was 1209±877 μg of folate. About 13.8% of pregnant women exhibited a lower intake of folate than that recommended during pregnancy. The average daily total choline intake of the pregnant women was 472±306 μg, about 50% below the appropriate intake reference value for total choline intake by pregnant women. Folate intake (r = -0.249, p = 0.010) and betaine intake (r = -0.252, p = 0.009) of the study cohort were inversely associated with lymphocytic LINE-1 methylation. According to a multiple linear regression analysis, maternal folate, betaine, and total choline intake respectively predicted 25% (beta: -0.257, p = 0.008), 31% (beta: -0.310, p = 0.001), and 18% (beta: -0.185, p = 0.058) of lymphocytic DNA methylation, respectively. No significant association of maternal methyl-donor intake with H19 methylation or plasma IGF-2 levels was observed. In general, the intake of methyl nutrients during pregnancy in Taiwan regulates the degree of methylation of the mother's genome, and its effects on fetal growth and development need to be further studied.

並列關鍵字

methyl donor intake ； LINE-1 methylation ； H19 methylation ； IGF-2 levels ； pregnancy