Effect of Obesity and Folic Acid Supplementation on Gene-specific DNA Methylation in Women of Reproductive Age
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Cell-type-specific DNA methylation
研究概览
简要总结
The objective of this study is to identify genes whose expression is potentially modifiable due to changes in folate intake and help delineate mechanisms accounting for the variability in individual response to folic acid supplementation. The study will be conducted in normal weight and obese women of childbearing age, supplemented for 8 weeks with 800 mcg/day folic acid.
It is hypothesized that (1) a change in folate status, induced by the supplementation, will influence the DNA methylation of specific genes and (2) the DNA methylation response to folic acid supplementation may differ between the normal weight and the obese women of childbearing age.
详细描述
This study will be conducted in two phases. An initial screening study will be performed to determine folate status, MTHFR677 genotype and body composition of potential participants of the intervention study. Both folate status and MTHFR677 genotype are known independent predictors of response to folic acid supplementation. Blood samples will be collected, after an overnight fast, for determination of serum folate concentration and for MTHFR677 genotyping. Body composition and 24-hr dietary recalls will also be conducted during the screening visit.
The second phase is an eight week supplementation trial with 800 mcg/day folic acid. Screened individuals determined to have a serum folate < 30 nmol/L (< 50th percentile of NHANES 1999-2004) and of the CC or CT genotype (for MTHFR677) will be eligible for inclusion in the supplementation trial. Participants will be instructed to avoid dietary supplements, fortified ready-to-eat cereals, and other high folate content foods during intervention. Blood samples will be collected, after an overnight fast, at baseline and after 4 and 8 weeks of supplementation for determination of primary (DNA methylation profile) and secondary (nutritional, metabolic and health status biomarkers) outcome measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Screening Phase:
- •Female 18-40 yr
- •Body Mass index 18.5 to 24.9 or > 30 kg/m2
- •Intervention Study:
- •Serum folate < 30 nmol/L
- •MTHFR677CC or MTHFR677CT genotype
排除标准
- •Currently pregnant, pregnancy within past 12 months
- •Greater than 2 previous pregnancies
- •Use of prescription drugs other than oral contraceptives
- •Chronic disease (diabetes, hypertension,epilepsy,cancer, kidney disease, CVD)
- •Acute illness (pneumonia, urinary tract infection, mononucleosis)
- •Use of antibiotics in past 30 days
- •Current smoker
- •Use of dietary supplements including multivitamins in past 30 days
- •Habitual consumption of fortified ready-to-eat cereals
- •Significant weight change in past 12 months
- •Typical alcohol consumption of 2 or more drinks per day
- •INTERVENTION: all above plus serum folate > 30 nmol/L; MTHFR677TT genotype
结局指标
主要结局
Cell-type-specific DNA methylation
时间窗: Baseline, 4 weeks and 8 weeks
Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from specific white blood cell types. Microarray analysis will be used to assess changes in multiple methylation sites within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.
Gene-specific DNA methylation
时间窗: Baseline, 4 weeks and 8 weeks
Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from whole blood . Microarray analysis will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.
次要结局
- Serum folate(Baseline, 4 weeks and 8 weeks)
- Red Blood Cell (RBC) Folate(Baseline, 4 weeks and 8 weeks)
- Body Composition(Baseline and 8 weeks)
研究者
Lynn B. Bailey, PhD
Department Head and Professor
University of Georgia