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白细胞介素-13/-4 和 Toll 样受体 10 与早产的关系。

Association of interleukin-13/-4 and toll-like receptor 10 with preterm births.

机构信息

Centre for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.

出版信息

Neonatology. 2009;96(3):175-81. doi: 10.1159/000210091. Epub 2009 Mar 31.

DOI:10.1159/000210091
PMID:19332998
Abstract

BACKGROUND

Preterm birth (PTB) is accompanied by an increased neonatal morbidity. The cause of PTB is multifactorial and the interplay between environmental and genetic factors - of mothers and newborns - determines the risk.

OBJECTIVES

We were interested to identify fetal genes predisposing to PTB in the German population.

METHODS

We started our study by screening 31 polymorphisms within 15 genes of 121 preterm infants born below 32 gestational weeks and 270 healthy controls. Genotyping was performed by restriction fragment length polymorphism. Statistical analyses used Armitage's trend test for single polymorphisms and FAMHAP for calculation of haplotypes.

RESULTS

No single polymorphism showed association with PTB; however, haplotypes of interleukin (IL)-13/IL-4 and Toll-like receptor (TLR)-10 were associated (p = 0.0001 and p = 0.0011, respectively). The association was further confirmed in an extended population of a total of 164 preterm infants. Furthermore, one polymorphism in IL-13 showed a weak association with PTB in this population (p = 0.031). Finally, we analyzed whether the cause of PTB, i.e. medically indicated cesarean section versus spontaneous PTB, affects association results and found evidence in favor of a separate analysis of both groups.

CONCLUSIONS

IL-13/IL-4 and TLR-10 might be involved in the genetics of PTB. The dissection of the genetic background may provide a deeper understanding of the pathophysiology of PTB and help to identify new drug targets for its prevention.

摘要

背景

早产(PTB)伴随着新生儿发病率的增加。PTB 的病因是多因素的,母亲和新生儿之间的环境和遗传因素相互作用决定了风险。

目的

我们有兴趣在德国人群中鉴定导致 PTB 的胎儿基因。

方法

我们通过对 121 名出生于 32 周以下的早产儿和 270 名健康对照者的 15 个基因中的 31 个多态性进行筛选,开始了我们的研究。基因分型通过限制性片段长度多态性进行。统计分析使用 Armitage 的趋势检验进行单多态性分析,使用 FAMHAP 进行单体型分析。

结果

没有单个多态性与 PTB 相关;然而,白细胞介素(IL)-13/IL-4 和 Toll 样受体(TLR)-10 的单体型与 PTB 相关(p = 0.0001 和 p = 0.0011)。在总共 164 名早产儿的扩展人群中进一步证实了这种关联。此外,在该人群中,IL-13 的一个多态性与 PTB 存在微弱关联(p = 0.031)。最后,我们分析了 PTB 的病因,即医学指征剖宫产与自发性 PTB 是否影响关联结果,发现有证据支持对两组进行单独分析。

结论

IL-13/IL-4 和 TLR-10 可能参与了 PTB 的遗传学。对遗传背景的剖析可能提供对 PTB 病理生理学的更深入理解,并有助于确定其预防的新药物靶点。

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