Pediatrics, Medical College of Wisconsin and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WI, USA.
J Perinatol. 2013 May;33(5):341-6. doi: 10.1038/jp.2012.120. Epub 2012 Oct 4.
To investigate whether single nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor (TLR) signaling pathway modulate susceptibility to preterm birth (PTB).
Prospective case-control study examining the contribution of nine TLR SNPs to PTB (<37 weeks) and PTB <32 weeks. Genotyping was done on neonatal blood using a multiplexed single-base extension assay. Chi-square test, Fischer's exact test and classification trees were used for data analysis.
Preterm infants (n=177) were more likely to be African American (P=0.02), and were more likely to be born to mothers who smoked (P=0.007), had pregnancy-induced hypertension (PIH; P=0.002) and placental abruption (P=0.0004) when compared with term infants (n=146). The TLR2, TLR4, TLR5, TLR9, nuclear factor-kappa B1 (NFκB1), NFκBIA and IRAK1 variants were not associated with PTB whereas the TIR domain receptor-associated protein (TIRAP) variant was more prevalent in term infants when compared with preterm infants born <32 weeks (P=0.004). PTB <32 weeks was more prevalent in infants without the TIRAP variant whose mothers had PIH and did not smoke (P=0.001). Presence of the TIRAP variant protected against PTB <32 weeks (P=0.015) in Caucasian infants.
In our study, a TLR pathway adapter variant (TIRAP (rs8177374)) protected against PTB<32 weeks, supporting our hypothesis that genetic variation in the innate immune signaling pathway contributes to altered risk of PTB.
探讨 Toll 样受体（TLR）信号通路基因编码的单核苷酸多态性（SNP）是否调节早产（PTB）易感性。
这是一项前瞻性病例对照研究，研究了九个 TLR SNP 对 PTB（<37 周）和 PTB<32 周的贡献。采用多重单碱基延伸法在新生儿血液中进行基因分型。采用卡方检验、Fisher 确切检验和分类树进行数据分析。
与足月婴儿（n=146）相比，早产儿（n=177）更可能是非洲裔美国人（P=0.02），且更可能出生于吸烟的母亲（P=0.007）、患有妊娠高血压（PIH；P=0.002）和胎盘早剥（P=0.0004）的母亲。TLR2、TLR4、TLR5、TLR9、核因子-κB1（NFκB1）、NFκBIA 和 IRAK1 变体与 PTB 无关，而 TIR 结构域受体相关蛋白（TIRAP）变体在足月婴儿中比出生于 32 周以下的早产儿更为常见（P=0.004）。与足月婴儿相比，在无 TIRAP 变体的婴儿中，PTB<32 周更为常见，这些婴儿的母亲患有 PIH 且不吸烟（P=0.001）。在没有 TIRAP 变体的婴儿中，如果母亲患有 PIH 且不吸烟，TIRAP 变体的存在可以预防 PTB<32 周（P=0.015）。在白人婴儿中，TIRAP 变体的存在保护他们免受 PTB<32 周的影响（P=0.015）。
在我们的研究中，TLR 通路接头变体（TIRAP（rs8177374））可预防 PTB<32 周，这支持了我们的假设，即先天免疫信号通路中的遗传变异会改变 PTB 的风险。
