非洲裔美国妇女的遗传变异与早产的关系

非洲裔美国妇女的遗传变异与早产的关系
Genetic variation associated with preterm birth in African-American women

Abstract
BACKGROUND:
Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery.
摘要
背景：
早产被认为是一种多因素的条件，但是，新的证据表明，个人之间的遗传变异可能有一个重要的作用。此前的研究表明，单核苷酸多态性与相关的基因相关的免疫系统，特别是产妇的炎症反应，可能与早产的风险增加。

OBJECTIVE:
The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women.
目的：
这项研究的目的是确定与自发性早产相关的单核苷酸多态性在非洲裔妇女的一个队列中的37周内。

STUDY DESIGN:
This is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term.
研究设计：
这是一个随机试验的二次分析，认为评估牙周疾病和早产。妇女们在3产前检查诊所6至20孕周之间入选2004年和收集，并使用自定义1536个单核苷酸阵列polymorphismgenotyping旨在评估参与炎症反应的基因分析，2007年孕产妇DNA样本之间。妇女被包括在这项研究，如果他们的自我认定为非裔美国人。我们排除妇女以多胎妊娠或指示早产。我们进行等位基因和基因型为基础的分析，以评估自发早产和标签的单核苷酸多态性之间的关联。我们使用logistic回归来调整我们基于基因型的分析之前，早产。在亚组分析中，我们比较谁在<34周妊娠交付给谁足月分娩的妇女的妇女。内的芯片，我们确定了祖先信息标记和中谁与那些谁足月分娩早产交付女性相比全球祖先估计。

RESULTS:
Of the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term.
结果：
833非裔美国妇女与基因型数据，77名妇女（9.2％）的研究有一个自发早产，而756的妇女足月分娩。在基于等位基因分析，有关的基因的蛋白激酶C-α（PRKCA）4单核苷酸多态性与自发早产<37周的风险增加有关，而单单核苷酸多态性与FMS相关的酪氨酸激酶1（FLT1）与自发早产<34周有关。基于基因分析显示有关PRKCA基因和自发性早产的单核苷酸多态性之间类似的协会。此外，单核苷酸多态性相关于矩阵基质金属蛋白酶-2（TIMP2）的金属蛋白酶-2（MMP2），组织抑制剂和白介素16（IL16）基因与自发早产<37周在基于基因型的分析相关联。相关MMP2遗传变异，基质金属蛋白酶-1（MMP1）和白血病抑制因子受体反义RNA 1（LIFR-AS1）基因与早产率较高<34周有关。祖先估计是谁了一个自发的早产和那些谁足月分娩妇女的相似。

CONCLUSION:
We identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.
结论：
我们确定了标签的单核苷酸多态性相关的7个基因，是关键的炎症，细胞外重塑，细胞信号，与自发早产在非洲裔妇女。具体来说，我们发现与PRKCA基因密切相关。在这些地区的基因组的遗传变异可能是重要的早产的发病机制。我们的研究结果应该在未来的基因组研究早产儿的设计考虑。

KEYWORDS:
genetics; inflammation; preterm birth
关键词：
遗传学；炎症；早产

原文全文：
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