Department of Histology, Embryology and Applied Biology, Centre of Molecular Genetics, University of Bologna, Bologna, Italy.
Int J Immunopathol Pharmacol. 2011 Apr-Jun;24(2 Suppl):1-5. doi: 10.1177/03946320110240S201.
The onset of embryonic malformations is greatly determined by the intrauterine environment, conditioned by maternal lifestyle, diet, drugs and medication intake, in addition to both foetal and maternal genotypes. Maternal C677T MTHFR genotype has been identified as important factor in cleft lip with or without cleft palate (CL/P) etiology. In the present study we evaluated the possible interaction between maternal methylenetetrahydrofolate reductase (MTHFR) and foetal ABCB1 genotypes. ABCB1 gene codes for a drug-transport pump in charge to protect the cell by extruding a variety of harmful exogens, but with a reduced activity in a folate-restricted condition. Maternal 677T genotype is translated in a reduced folate availability for the developing embryo who consequently may becomes more exposed to external insults. A family based association analysis was performed to test the effect of ABCB1 polymorphisms in clefting, in the whole sample and in the stratified sample accordingly to maternal MTHFR genotype. No evidence of association between ABCB1 polymorphisms and CL/P was detected. This suggests that ABCB1 or ABCB1-MTHFR feto-maternal interaction could have no effect in orofacial clefting or could play a role in a limited number of cases.
胚胎畸形的发生在很大程度上取决于宫内环境，受母体生活方式、饮食、药物和药物摄入以及胎儿和母体基因型的影响。母体 C677T MTHFR 基因型已被确定为唇裂伴或不伴腭裂（CL/P）病因的重要因素。在本研究中，我们评估了母体亚甲基四氢叶酸还原酶（MTHFR）和胎儿 ABCB1 基因型之间可能存在的相互作用。ABCB1 基因编码一种药物转运泵，负责通过排出各种有害物质来保护细胞，但在叶酸受限的情况下其活性降低。母体 677T 基因型导致发育中的胚胎叶酸供应减少，从而使胚胎更容易受到外部伤害。进行了基于家庭的关联分析，以测试 ABCB1 多态性在整个样本和根据母体 MTHFR 基因型分层样本中的唇裂效应。未发现 ABCB1 多态性与 CL/P 之间存在关联。这表明 ABCB1 或 ABCB1-MTHFR 胎儿-母体相互作用可能对口腔裂无影响，或者仅在少数情况下发挥作用。
