NUTRIENT BIOMARKERS, GENES AND OROFACIAL CLEFTS

描述（改编自申请人的描述） 世界上最常见的出生缺陷之一， 其主要原因和发生的地区差异。在我们以前 在菲律宾的研究中，我们最近发现了生物化学证据， 母亲的维生素B-6和叶酸水平独立地与 裂的风险增加，MTHFR C677 T突变与 同时降低了裂开的风险。我们建议详细说明这些方法， 研究营养与基因的相互作用，并将其应用于基于人群的案例中， 犹他州口面裂的对照研究，具体目标如下： (1)口面裂儿童（n = 686）将由国家确定- 广泛的犹他州出生缺陷登记处和他们的母亲将被招募为病例 受试者;（2）将随机选择无唇腭裂的儿童（n= 686） 来自犹他州的出生证明和他们的母亲将被招募作为对照 参与者;（3）将收集饮食模式、吸烟、饮酒 使用和其他接触使用电话采访和邮寄 （4）从母亲体内抽取静脉血样， 处理，并测定维生素B-6和叶酸的生化指标 （5）准备母亲、儿童和父亲的DNA， 对与维生素B-6和叶酸相关的多态性遗传标记进行基因分型 新陈代谢. 本研究将探讨以下假设：（1）母亲维生素B-6缺乏 状态与口面裂风险增加独立相关; (2)母亲叶酸水平低与叶酸水平升高独立相关 （3）MTHFR C677 T等位基因与口面裂的风险相关。 降低了开裂的风险。此外，等位基因变体之间的关联 其他叶酸和维生素B-6相关的遗传标记和风险 （4）营养成分和候选基因 以上提到的相互作用，相加或相乘，以增加风险 口面裂 我们的多学科研究的母亲营养和风险的裂缝， 与代谢途径相关的基因背景可能会导致更好的 了解口面裂的成因及预防。

DESCRIPTION (Adapted from the Applicant's Description) Orofacial clefts are among the most common birth defects in the world yet little is known about their major causes and regional differences in occurrence. In our previous studies in the Philippines we recently found biochemical evidence that poor vitamin B-6 and folic acid levels of mothers are independently associated with increased risks of clefting and that the MTHFR C677T mutation is associated with a reduced risk of clefting. We propose to elaborate these methods for studying nutrient-gene interactions and apply them in a population-based case- control study of orofacial clefts in Utah with the following specific aims: (1) Children with orofacial clefts (n = 686) will be ascertained by the state- wide Utah birth defects registry and their mothers will be recruited as case participants; (2) Children without clefts (n= 686) will be randomly selected from Utah birth certificates and their mothers wIll be recruited as control participants; (3) Data will be collected on dietary patterns, smoking, alcohol use and other exposures using telephone-based interviews and mailed questionnaires; (4) Venous blood samples will be drawn from mothers, rapidly processed, and assayed for biochemical indicators of vitamin B-6 and folate status; (5) DNA from mothers, children, and fathers will be prepared and genotyped for polymorphic genetic markers related to vitamin B-6 and folate metabolism. The following hypotheses will be addressed: (1) Poor maternal vitamin B-6 status is independently associated with increased risk of orofacial clefts; (2) Poor maternal folate status is independently associated with increased risk of orofacial clefts; (3) The MTHFR C677T allele is associated with a reduced risk of clefting. In addition the association between allelic variants of other folate- and vitamin B-6-related genetic markers and the risk of orofacial clefts will be examined; (4) The nutrients and candidate genes mentioned above interact, additively or multiplicatively, to increase the risk of orofacial clefting. Our multidisciplinary study of maternal nutrition and risk of clefting in the context of genes related to metabolic pathways may lead to a better understanding of the causes and prevention of orofacial clefts.