Toll样受体4启动子区基因多态性及环境因素与复发性流产关系研究

The association of ss77136219 A > G polymorphism in the promoter of TLR4 gene with the risk of unexplained recurrent miscarriages

目的:研究Toll样受体-4(TLR4)启动子区基因多态性及环境因素与南方女性不明原因复发性流产的关系。方法:对183例不明原因复发性流产患者及240例健康妇女(对照)进行外周血DNA分型及环境因素问卷调查,比较各因素发生的频率差异,同时采用免疫印记及实时荧光定量PCR方法,检测位点TLR4-ss77136219A>G变异与mRNA及蛋白表达的关系。结果:在不明原因复发性流产组与对照组BMI值、年龄及TLR4-ss77136219A>G基因型间差异有统计学意义;TLR4-ss77136219A>G变异上调TLR4的mRNA及蛋白表达。结论:TLR4启动子区遗传变异及环境因素均导致不明原因复发性流产可能性增高。

Objective ： To examine the association of two common putative functional single nucleotide polymorphism （SNPs） in the promoter of toll like receptor 4 （ TLR - 4 ） with the risk of unexplained recurrent miscarriage （URSA） in a Chinese pop-ulation. Methods： We recruited 183 URSA women and 240 miscarriage-free controls in this study. The environmental factors were studied with a questionnaire survey, and two SNPs in the TLR4 promoter （rs10983755 G 〉 A, ss77136219 A 〉 G） were examined by real - time PCR and immunoblotting. Results： The polymorphism of ss77136219A 〉 G in the TLR4 promoter was associated with an increased risk of URSA, and women with higher BMI （ ≥ 24.0 kg/m2 ） and older age （ ≥ 35 years old） were also found to be at higher risk of URSA. The polymorphism of ss77136219A 〉 G in the TLR4 promoter up - regulated the expression of TLR4 and its mRNA in human decidua. Conclusions： The TLR4-promoter-ss77136219 G genotype may be a risk factor of URSA. Higher BMI （ ≥24.0 kg/m2） and older age （ ≥35 years old） can also increase the incidence of URSA in Chinese women.