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目的探讨绒毛滋养细胞HLA-C基因及其表达与原因不明复发性流产(URSA)易感性的关系。方法留取2006年1月至2008年2月在山东大学附属省立医院生殖中心就诊的URSA患者(38例,URSA组)及同期正常早孕妇女(35例,对照组)的绒毛组织,DNA测序法分析绒毛滋养细胞HLA-C1、HLA-C2基因,荧光实时定量PCR法分析绒毛滋养细胞HLA-C1mRNA、HLA-C2mRNA的相对表达量。结果 (1)两组基因HLA-C1、HLA-C2在绒毛组织中呈不平衡表达,以HLA-C1基因占明显优势。URSA组HLA-C1基因的频率为66.67%,对照组HLA-C1基因的频率为81.03%,两组相比差异无统计学意义(P=0.657);URSA组HLA-C2基因的频率为33.33%,对照组HLA-C2基因的频率为18.97%,两组相比差异有统计学意义(P=0.007)。(2)URSA组绒毛滋养细胞HLA-C1mRNA的相对表达量(59.39±13.43)显著低于对照组(95.43±28.78),差异有统计学意义(P=0.016);URSA组绒毛滋养细胞HLA-C2mRNA的相对表达量(68.22±18.73)与对照组(48.33±17.30)比较,差异无统计学意义(P=0.321)。结论绒毛滋养细胞HLA-C2基因高表达,HLA-C1、HLA-C2基因表达失衡可能是引起URSA发病的免疫遗传学因素之一。
Objective To investigate the relationship between the expression of HLA-C gene in villus trophoblast cells and the susceptibility to unexplained recurrent spontaneous abortion (URSA). Methods URSA patients (38 cases, URSA group) and normal early pregnant women (35 cases, control group) were enrolled in the Reproductive Center of Provincial Hospital Affiliated to Shandong University from January 2006 to February 2008, HLA-C1 and HLA-C2 genes of villous trophoblast cells were analyzed by real-time PCR. The relative expression of HLA-C1 mRNA and HLA-C2 mRNA in villus trophoblast cells was analyzed by real-time quantitative PCR. Results (1) The HLA-C1 and HLA-C2 genes in both groups were imbalanced in villus tissues, and HLA-C1 gene was predominant. The frequency of HLA-C1 gene was 66.67% in URSA group and 81.03% in control group, there was no significant difference between the two groups (P = 0.657). The frequency of HLA-C2 gene in URSA group was 33.33% . The frequency of HLA-C2 gene in control group was 18.97%, there was significant difference between the two groups (P = 0.007). (2) The relative expression level of HLA-C1 mRNA in URSA group (59.39 ± 13.43) was significantly lower than that in control group (95.43 ± 28.78) (P = 0.016). The HLA-C2 mRNA in URSA group (68.22 ± 18.73) compared with the control group (48.33 ± 17.30), the difference was not statistically significant (P = 0.321). Conclusion The HLA-C2 gene of villus trophoblast cells is highly expressed. The imbalance of HLA-C1 and HLA-C2 gene expression may be one of the immunological genetic factors that cause URSA.