Su Ning, Wang Hongdan, Zhang Bowei, Kang Yiqing, Guo Qiannan, Xiao Hai, Yang Hecai, Liao Shixiu
Department of Obstetrics and Gynecology, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
Henan Medical Genetics Institute, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.
Exp Ther Med. 2018 Jan;15(1):327-337. doi: 10.3892/etm.2017.5406. Epub 2017 Oct 31.
The underlying mechanism of recurrent spontaneous abortion (RSA) has remained elusive for many years. Several previous studies have suggested that the killer cell immunoglobulin receptor (KIR) gene family is associated with RSA, however, it is not clear exactly how. The present study detected KIR and human leukocyte antigen-C (HLA-C) genes in 110 Han Chinese women with unexplained RSA and 105 Han Chinese healthy females. The aim of the present study was to determine if certain genotypes were more susceptible to the occurrence of miscarriage. The frequency of KIR genes and different KIR haplotypes in the 2 groups demonstrated no statistical differences. However, in women who had miscarried ≥3 times, the frequency of KIR3DL1 was significantly reduced and the BB haplotype frequency was significantly higher compared with the control group. HLA-C2C2 was significantly increased in the KIR AB and KIR BB groups in the RSA groups compared with the control group. The women in the RSA group who had a homozygous HLA-C2C2 had a significantly higher frequency of the 2DS1 gene compared with the control group. The reduction of inhibitory gene and increased activation combinations may induce the activation of uterine natural killer cells, which may reduce the probability of fetal survival. To the best of our knowledge, the present study is the first report demonstrating the association between maternal KIR and HLA-C genes and RSA in women of a Han Chinese ethnicity. The present study revealed that females who miscarry ≥3 times may be used as selection criteria for RSA and so may exhibit higher research value.
复发性自然流产(RSA)的潜在机制多年来一直难以捉摸。此前的多项研究表明,杀伤细胞免疫球蛋白受体(KIR)基因家族与RSA有关,然而,具体关联方式尚不清楚。本研究检测了110名原因不明的RSA汉族女性和105名汉族健康女性的KIR和人类白细胞抗原-C(HLA-C)基因。本研究的目的是确定某些基因型是否更易发生流产。两组中KIR基因和不同KIR单倍型的频率无统计学差异。然而,与对照组相比,流产≥3次的女性中,KIR3DL1的频率显著降低,BB单倍型频率显著升高。与对照组相比,RSA组中KIR AB和KIR BB组的HLA-C2C2显著增加。RSA组中HLA-C2C2纯合子的女性与对照组相比,2DS1基因的频率显著更高。抑制基因的减少和激活组合的增加可能会诱导子宫自然杀伤细胞的激活,这可能会降低胎儿存活的概率。据我们所知,本研究是首次报道汉族女性母体KIR和HLA-C基因与RSA之间的关联。本研究表明,流产≥3次的女性可作为RSA的筛选标准,因此可能具有更高的研究价值。