Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Eur J Clin Nutr. 2010 Mar;64(3):266-73. doi: 10.1038/ejcn.2009.138. Epub 2009 Nov 25.
BACKGROUND/OBJECTIVES: Riboflavin is a cofactor for the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme involved in the homocysteine pathway. The aim of this study was to investigate the effects of maternal riboflavin intake and two MTHFR polymorphisms (677C>T; Ala222Val and 1298A>C; Glu429Ala substitutions) on the biomarkers of the homocysteine pathway, and investigate the risk of having offspring with an orofacial cleft (OFC).
SUBJECTS/METHODS: In a case-control study design, dietary riboflavin intake and the MTHFR 677C>T and 1298A>C polymorphisms were evaluated in 123 OFC and 108 control mothers by using food frequency questionnaires and blood samples. Homocysteine (tHcy), folate and vitamin B12 concentrations in blood were analyzed in 70 cases and 68 controls. Linear and logistic regression analyses were applied.
At 14 months postpartum riboflavin intake and MTHFR 677C>T and 1298A>C genotypes were not significantly different between cases and controls. The 677TT genotype showed lower folate concentrations compared to C-allele carriers with a mean difference of 2.8 nmol/l in serum and 174 nmol/l in red blood cell (both P's=0.01). Every mg per day increase of dietary riboflavin intake was positively associated with increase in vitamin B12 concentration by 52.1% (P<0.01). This effect was most pronounced in MTHFR 677TT homozygotes (205.1%, P=0.03). The riboflavin-adjusted MTHFR 677TT and 1298CC genotypes showed a trend toward an increasing risk for OFC, adjusted odds ratio 1.7 (confidence interval (95% CI), 0.7-4.5) and 1.6 (95% CI, 0.7-4.2), respectively.
Maternal riboflavin intake is significantly associated with biomarkers of the homocysteine pathway, with the strongest effects in MTHFR 677TT homozygotes. The maternal risk of having OFC offspring, however, is not associated with dietary riboflavin intake.
背景/目的：核黄素是参与同型半胱氨酸途径的 5,10-亚甲基四氢叶酸还原酶（MTHFR）酶的辅因子。本研究旨在探讨母体核黄素摄入和两种 MTHFR 多态性（677C>T；Ala222Val 和 1298A>C；Glu429Ala 取代）对同型半胱氨酸途径生物标志物的影响，并探讨生育唇腭裂（OFC）后代的风险。
受试者/方法：在病例对照研究设计中，通过食物频率问卷和血液样本评估了 123 例 OFC 和 108 例对照母亲的核黄素摄入量和 MTHFR 677C>T 和 1298A>C 多态性。分析了 70 例病例和 68 例对照的血液同型半胱氨酸（tHcy）、叶酸和维生素 B12 浓度。应用线性和逻辑回归分析。
产后 14 个月，病例组和对照组之间核黄素摄入量和 MTHFR 677C>T 和 1298A>C 基因型无显着差异。677TT 基因型的叶酸浓度明显低于 C 等位基因携带者，血清中位数差异为 2.8 nmol/L，红细胞中位数差异为 174 nmol/L（均 P=0.01）。每日每毫克核黄素摄入量增加与维生素 B12 浓度增加呈正相关，增加 52.1%（P<0.01）。这种作用在 MTHFR 677TT 纯合子中最为明显（205.1%，P=0.03）。调整核黄素后，MTHFR 677TT 和 1298CC 基因型的 OR 值呈上升趋势，OR 值分别为 1.7（95% CI，0.7-4.5）和 1.6（95% CI，0.7-4.2）。
母体核黄素摄入量与同型半胱氨酸途径的生物标志物显着相关，在 MTHFR 677TT 纯合子中作用最强。然而，母体生育 OFC 后代的风险与饮食核黄素摄入无关。
