Study of the Association of Blood Folate Metabolites with Polymorphisms of Folic Acid Metabolic Pathway Genes in Pregnan Women

Autor: Yu-Chao Chen, 陳昱超
Rok vydání: 2008
Druh dokumentu: 學位論文 ; thesis
Popis: 96
Background Folate is one of vitamin B complex. Epidemiological studies reveal the incidence of pregnancy complications and newborn neural tube defect in folate-insufficient pregnant women. Thereby, it is recommended to boost higher dose of folic acid during the first trimester of pregnancy for the prevention from unwilling complications. Combining the knowledge of metabolomics and pharmacogenomics, we tried to study the effect of folate intake in pregnant women and genetic impact from the view point of folate metabolites. Methods Healthy and pregnant women in outpatient service of Eugene Clinic were enrolled in our study. We collected blood samples during their routine blood drawn for LC/MS-MS and HPLC detection of folate metabolites. The use of folate supplement, basic demographic data and dietary preference were surveyed by a questionary. Genotypes of the selected genes including MTHFR, MTR, MTRR, MTHFD1, ALDH1L1, AMT, FOLH1and BHMT were determined using SNPstream system. Results The 89 participants include 7 healthy non-pregnant women, 26 pregnant women without folate supplement and 56 pregnant women with regular folate intake. We successfully detected FA, 5MeTHF, 5FoTHF, 5,10CHTHF, and plasma homocysteine concentration. In pregnant women receiving daily folate supplement, erythrocyte 5MeTHF concentration increases with the gestation age. Although plasma and erythrocyte folate concentration decrease with time in pregnant women without folate supplement, it is not statistically significant (p> 0.05). Folate supplement did not make difference in plasma homocysteine levels of pregnant women. However there’s an inverse relation between plasma folate metabolites and homocysteine. Among18 successfully determined genes, genotypes of MTHFR, MTR, MTRR, ALDH1L1, AMT, FOLH1, BHMT genes were correlated to the concentrations of folate metabolites. The 5FoTHF/5,10CHTHF ratio is correlated to the distribution of genotypes of MTHFR, MTRR, and ALDH1L1. Conclusion Folate supplement importantly changed 5MeTHF concentration compared to the other folate metabolites and elevated plasma 5MeTHF immediately. In the pregnant women with regular folate supplement, erythrocyte 5MeTHF level increases with gestational age. It might be due to the increase during pregnancy in folate uptake capacity via altered hormone regulation. In pregnant women without folate supplement, levels of folate metabolites varied, which was associated with genotypes of MTHFR, MTR, MTRR, ALDH1L1, and AMT. The 5FoTHF/5,10CHTHF ratio is relatively low in pregnant women carrying heterozygotic SNPs of MTHFR, MTRR, ALDH1L1 genes. It may be as a maker for evaluating genetic effects on folate maintenance.
Databáze: Networked Digital Library of Theses & Dissertations
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