NUTRIENT BIOMARKERS, GENES AND OROFACIAL CLEFTS

描述(改编自申请者的描述)口腔裂隙 世界上最常见的出生缺陷之一，但人们对此知之甚少 它们的主要成因和发生的地区差异。在我们之前的 在菲律宾的研究中，我们最近发现了生化证据， 母亲的维生素B-6和叶酸水平与 MTHFR C677T突变与唇裂风险增加有关 同时降低了裂伤的风险。我们建议详细说明这些方法，以 研究营养-基因相互作用并将其应用于基于人群的病例- 犹他州口腔裂伤对照研究的具体目标如下： (1)患有口裂的儿童(n=686)将由国家- 犹他州出生缺陷登记处和他们的母亲将被招募为病例 研究对象：(2)随机抽取686名无唇裂儿童 来自犹他州的出生证明和他们的母亲将被招募为对照 参与者；(3)将收集有关饮食模式、吸烟、饮酒的数据 通过电话采访和邮寄的使用和其他曝光 问卷调查；(4)将迅速从母亲身上采集静脉血样 加工，并检测维生素B-6和叶酸的生化指标 (5)来自母亲、孩子和父亲的DNA将准备好并 维生素B-6和叶酸相关多态遗传标记的基因分型 新陈代谢。 我们将提出以下假设：(1)孕妇维生素B-6缺乏 社会地位与口腔裂伤风险的增加独立相关； (2)母亲叶酸状况差与叶酸水平升高独立相关。 (3)亚甲基四氢叶酸还原酶C677T等位基因与 降低了裂伤的风险。此外，等位基因变异之间的关联 其他与叶酸和维生素B-6相关的遗传标记的风险 将检查口腔裂隙；(4)营养物质和候选基因 上面提到的相互作用，相加或相乘，增加了风险 口腔裂伤的症状。 我们对孕妇营养与婴幼儿唇裂风险的多学科研究 与代谢途径相关的基因背景可能会导致更好的 了解口腔颌面裂的原因及预防。

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.