Du Mengxuan, Gu Heng, Li Yanqiu, Huang Liyan, Gao Mengge, Xu Hang, Deng Huaqian, Zhong Wenyao, Liu Xiaohua, Zhong Xingming
NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510600, Guangdong Province, China.
Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510630, Guangdong Province, China.
Open Life Sci. 2022 Nov 14;17(1):1443-1450. doi: 10.1515/biol-2022-0518. eCollection 2022.
Unexplained recurrent spontaneous abortion (URSA) is a major concern in reproductive medicine. Neutrophil cytosolic factor 1 () polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases. We investigated the association of the missense single nucleotide polymorphism (SNP) rs201802880 (NCF1-339) in with URSA and explored its function. We performed NCF1-339 SNP genotyping of samples from 152 Chinese patients with URSA and 72 healthy controls using nested PCR and TaqMan assays. ROS production and RELA (NF-κB subunit) expression in the blood of participants with different NCF1-339 genotypes were determined. The frequencies of the wild-type (GG) and mutant (GA) genotypes remarkably differed between the URSA and control groups. The mutant genotype was associated with an increased risk of recurrent abortion. Furthermore, ROS levels in the URSA group with the GG genotype were significantly higher than those in the group with the GA genotype ( < 0.05). RELA expression in URSA patients with the GA genotype was considerably higher than that in control individuals with the GG genotype. These findings indicate that mutations in may increase the risk of URSA via the NADP/ROS/NF-κB signaling pathway, which has implications for the diagnosis and treatment of URSA.
不明原因复发性自然流产（URSA）是生殖医学中的一个主要问题。导致活性氧（ROS）产生减少的中性粒细胞胞质因子1（）多态性与自身免疫性疾病密切相关。我们研究了中的错义单核苷酸多态性（SNP）rs201802880（NCF1-339）与URSA的关联，并探讨了其功能。我们使用巢式PCR和TaqMan分析对152例中国URSA患者和72例健康对照的样本进行了NCF1-339 SNP基因分型。测定了不同NCF1-339基因型参与者血液中的ROS产生和RELA（NF-κB亚基）表达。URSA组和对照组之间野生型（GG）和突变型（GA）基因型的频率有显著差异。突变基因型与复发性流产风险增加相关。此外，GG基因型的URSA组中的ROS水平显著高于GA基因型组（<0.05）。GA基因型的URSA患者中的RELA表达明显高于GG基因型的对照个体。这些发现表明，中的突变可能通过NADP/ROS/NF-κB信号通路增加URSA的风险，这对URSA的诊断和治疗具有重要意义。
