雌激素受体基因多态性与女性类风湿关节炎相关性的研究

Association between estrogen receptor gene polymorphisms and rheumatoid arthritis in Chinese women

目的分析雌激素受体(ER)基因XbaⅠ和PvuⅡ酶切多态性在女性类风湿关节炎(RA)中的分布,探讨其与人类白细胞抗原(HLA)-DRβ1*04基因亚型、类风湿因子(RF)以及RA患者临床表现的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,对81例女性RA患者和146名女性正常对照者的ER基因(XbaⅠ、PvuⅡ位点)进行分型,并计算基因分布频率。分析患者的HLA-DRβ1*04基因亚型、RF以及临床表现与ER基因多态性之间的关系。结果女性RA患者的ER基因X、P基因频率均明显高于健康对照组,ER基因的XX和PP基因亚型的阳性率分别高于正常对照组(P<0.05)。而RA患者的xx基因亚型的阳性率明显低于健康对照组(P<0.05)。RA患者XXPP基因型的阳性率明显高于健康对照组,而xxpp基因型的阳性率明显低于健康对照组(P<0.05)。携带PP基因型的RA患者HLA-DRβ1*04基因亚型的阳性率明显升高(P<0.05)。ER基因中pp基因型、XXpp和xxPP基因型的患者关节受累数明显增高(P<0.05)。结论女性RA患者ER基因的X和P的基因频率表达明显增高。ER基因酶切多态性分析中,XX、PP及XXPP基因型可能与女性RA的易感性相关。PP基因型可能与HLA-DRβ1*04基因有一定的相关性,pp基因型、XXpp和xxPP基因型可能与RA关节病变的程度相关。

Objective To investigate the estrogen receptor (ER) gene polymorphisms in female patients with rheumatoid arthritis (RA). To study the relationship between the ER gene subtypes and HLA-DRβ1*04 genotype, rheumatoid factor, clinical features of rheumatoid arthritis. Methods XbaⅠ and PvuⅡrestriction fragment length polymorphisms of ER gene were analysed in 81 female patients with RA and 146 female controls. ER gene typing was preformed using PCR-RELP techniques. The clinical features, RF and HLA-DRβ1*04 genotyp between different motif of ER gene were analyzed. Results Compared with health controls, the frequency of X and P gene in female patients with RA were significantly increased (P<0.05). The frequency of XX and PP genotype of ER gene were higher in RA female patients than those in normal controls, while the frequency of xx genotype were lower than those in normal controls (P<0.05). The frequency of XXPP genotype of ER gene polymorphisms were significantly increased, while the frequency of xxpp genotype were significantly decreased (P<0.05). The positive rate of HLA-DRβ1*04 genotype in the patients with PP genotype was higher than pp genotype and Pp genotype (P<0.05). The number of joint involved increased in the patients with pp genotype? XXpp and xxPP genotype (P<0.05). Conclusion The results suggest that X and P genotype are significantly increased in female patients with RA in China. The XX, PP and XXPP genotype of ER gene may be associated with RA in the female patients. The ER-PP genotype may have closely relationship with HLA-DRβ1*04 genotype. The arthropathy severity of RA is related to the ER-pp, XXpp and xxPP genotype.