Nutrition and the Genetics of Prematurity

描述（由申请人提供）：该项目涉及导致早产种族差异的基因-环境相互作用。我们已经发现，在怀孕早期，下生殖道炎症环境有特定的变化，使妇女容易早产。我们还发现，这些下生殖道炎症环境的改变在黑人妇女中更常见，而且黑人妇女比白色妇女更有可能拥有与感染相关的早产相关的细胞因子启动子基因多态性。了解环境和基因-环境相互作用对炎症的影响对于了解早产的种族差异至关重要。营养状况对免疫力的影响具有流行病学和生物学双重原因。我们认为，对营养状况的生物反应可能通过下生殖道免疫力的变化影响早产，而下生殖道免疫力的变化易导致上生殖道感染/炎症。我们还假设，炎症基因型影响下生殖道炎症的性质，发生在怀孕前和怀孕期间营养状况不佳的妇女，这些影响进一步修改种族。我们的目的是确定围孕期和孕期的营养状况是否与早产有关。为此，我们将在4年内招募1200名女性参与前瞻性队列研究。营养状况由膳食摄入、母体血液和指甲中的营养生物标志物、孕前体重指数和体重增加来表示。我们的目标是确定怀孕期间不利的营养状况是否会促进下生殖道炎症环境，从而增加早产的风险。炎症环境由重要的宫颈细胞因子、阴道pH和10周前和24-28周时的阴道中性粒细胞代表。我们的目的是评估炎症基因多态性是否改变营养对下生殖道炎症和早产风险的影响，从而建立一个基因-环境相互作用。将从母体血液中提取DNA，对所有受试者进行多态性基因分型，以确定是否存在改变营养状态对下生殖道免疫和早产风险影响的基因型或基因型模式。最后，我们的目标是确定种族如何改变炎症基因多态性和营养对下生殖道免疫和早产风险之间的相互作用。

DESCRIPTION (provided by applicant): This project addresses gene-environment interactions that contribute to the racial disparity in preterm birth. We have found that there are specific changes in the lower genital tract inflammatory milieu early in pregnancy that predispose women to preterm birth. We have also found that these alterations in the lower genital tract inflammatory milieu are more common among black women, and that black women are more likely than white women to possess cytokine promoter gene polymorphisms that are related to infection- related preterm birth. Understanding the influence of environment and gene-environment interactions on inflammation is critical to understanding the racial disparity in preterm birth. Nutritional status' influence on immunity has both epidemiological and biological plausibility. We posit that biologic responses to nutritional status may affect preterm birth via changes in lower genital tract immunity that predispose to upper genital tract infection/inflammation. We also hypothesize that inflammatory genotype influences the nature of the lower genital tract inflammation that occurs among women with an unfavorable nutritional status before and during pregnancy, and that these effects are further modified by race. We aim to determine if nutritional status periconceptionally and during pregnancy is associated with preterm birth. To this end, we will enroll 1200 women over 4 years in a prospective cohort study. Nutritional status is represented by dietary intake, nutritional biomarkers in maternal blood and nails, pre-pregnancy body mass index, and weight gain. We aim to determine if unfavorable nutritional status in pregnancy promotes a lower genital tract inflammatory milieu that increases the risk of preterm birth. Inflammatory milieu is represented by important cervical cytokines, vaginal pH, and vaginal neutrophils prior to 10 weeks and at 24-28 weeks. We aim to evaluate whether inflammatory gene polymorphisms alter the impact of nutrition on lower genital tract inflammation and on the risk of preterm birth, thus establishing a gene-environment interaction. DNA will be extracted from maternal blood to genotype all subjects for polymorphisms in order to determine if there are genotypes or genotype patterns that modify the impact of nutritional status on lower genital tract immunity and on the risk of preterm birth. Finally, we aim to identify how race modifies the interaction between inflammatory gene polymorphisms and nutrition on lower genital tract immunity and the risk of preterm birth.