妊娠期人巨细胞病毒活动性感染与外周血 TLR2基因单核苷酸多态性的关联

Association between peripheral blood TLR2 gene single nucleotide polymorphism and active human cytomegalovirus infection during pregnancy

目的探讨妊娠期人巨细胞病毒(HCMV)活动性感染与外周血Toll样受体2(TLR2)基因单核苷酸多态性的关联。方法选择新疆医科大学第一附属医院妇产科2018年3月-2020年3月出生的活动性HCMV感染新生儿和潜伏性HCMV感染新生儿各80例,以其母亲作为研究对象,分别纳入活动性感染组和潜伏性感染组,根据相关标准,将活动性感染组进一步分为原发感染组和再激活感染组。针对TLR2基因rs1898830、rs3775291和rs179008位点设计特异性引物,采用Taqman荧光探针法检测三个位点基因分型。结果活动性感染组rs1898830位点AA基因型频率高于潜伏感染组,差异具有统计学意义(P<0.05);两组rs3804100、rs179008位点基因型分布比较,无统计学差异;活动性感染组rs1898830位点A等位基因频率高于潜伏感染组,G等位基因频率低于潜伏感染组,差异具有统计学意义(P<0.05);两组rs3804100、rs179008位点等位基因频率比较,无统计学差异;多元Logistic回归分析,结果显示携带rs1898830 AA基因型、rs1898830 A等位基因为孕期HCMV活动性感染的独立危险因素(P<0.05);原发感染组与再激活感染组rs1898830基因型分布比较,无统计学差异。结论 rs1898830 AA基因型是妊娠期巨细胞病毒活动性感染的危险基因型,A等位基因为危险等位基因,但该位点多态性与原发感染或再激活感染无关,相关机制有待进一步研究。

OBJECTIVE To explore the association between Toll receptor 2(TLR2) gene single nucleotide polymorphisms in peripheral blood and active human cytomegalovirus(HCMV) infection during pregnancy. METHODS Totally 80 neonates with active HCMV infection and 80 neonates with latent HCMV infection who were treated in department of obstetrics and gynecology of the First Affiliated Hospital of Xinjiang Medical University from Mar 2018 to Mar 2020 were enrolled in the study, their mothers were recruited as the study subjects and were respectively assigned as the active infection group and the latent infection group, and the study subjects of the active infection group were further divided into the primary infection group and the reactivated infection group according to the relevant criteria. The specific primers were designed for the rs1898830, rs3775291 and rs179008 loci of the TLR2 gene, and the genotypes of the three loci were detected by using Taqman fluorescent probe. RESULTS The frequency of AA genotype at the rs1898830 locus was significantly higher in the active infection group than in the latent infection group(P<0.05).There were no significant differences in the genotypes at rs3804100 and rs179008 loci between the two groups. The frequency of allele A at rs1898830 locus was significantly higher in the active infection group than in the latent infection group, the frequency of allele G of the active infection group was significantly lower than that of the latent infection group, and there was significant difference(P<0.05). There were no significant differences in the frequencies of alleles at rs3804100 and rs179008 loci between the two groups. Multivariate logistic regression analysis showed that AA genotype at rs1898830 and allele A at rs1898830 A were independent risk factors for active HCMV infection during the pregnancy(P<0.05). There were no significant differences in the genotypes at rs1898830 between the primary infection group and the reactivated infection group. CONCLUSION The genotype AA at rs1898830 locus is a risk genotype for active HCMV infection during the pregnancy, the allele A is a risk allele, however, the polymorphism of the locus is not associated with the primary infection or reactivated infection, the related mechanisms need to be further studied.