Foxp3基因多态性与原因不明复发性自然流产易感性的关系  

Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplainedrecurrent spontaneous abortion

作　　者：吴再归[1] 游泽山[1] 张彩[1] 李珠玉[1] 苏秀梅 张秀明 李银广[1] 

机构地区：[1]中山大学附属第一医院妇产科,广州510080 [2]干细胞与组织工程研究所 [3]广东省潮州市人民医院妇产科

出　　处：《中华妇产科杂志》2011年第10期763-768,共6页Chinese Journal of Obstetrics and Gynecology

基　　金：广东省科技计划（20088030301072、20088030301096）

摘　　要：目的探讨转录因子Foxp3基因多态性与原因不明复发性自然流产（URSA）易感性的关系。方法分别采用PCR-限制性片段长度多态性技术（针对Foxp3基因的rs3761548、rs2294021位点）和PCR-等位基因特异性扩增技术（针对rs2232365、rs5902434位点），检测146例URSA患者（URSA组）和112例健康妇女（对照组）血中Foxp3基因上述4个位点的基因型分布。结果（1）rs3761548和rs2232365位点：URSA组和对照组妇女中，rs3761548位点的3种基因型频率分别为C／C基因型10．3％、22．3％，A／C基因型38．4％、40．2％，A／A基因型51．4％、37．5％，rs2232365位点的基因型频率分别为A／A基因型5．5％、15．2％，A／G基因型47．9％、50．0％，G／G基因型46．6％、34．8％，分别比较，差异均有统计学意义（P〈0．05）；rs3761548A和rs2232365G等位基因明显增加URSA的发病风险（OR=1．73、1．61，P均〈0．05）。（2）rs5902434位点：3种基因型在两组的分布分别为ATT/ATT基因型7．5％、12．5％，del／ATT基因型42．5％、50．0％，del／del基因型50．0％、37．5％，分别比较，差异均无统计学意义（P=0．10）；但缺失型等位基因del频率URSA组明显高于对照组（分别为71．2％、62．5％；OR=1．49，P=0．04）。（3）rs2294021位点：3种基因型（C／C、T／C、rr／T）和T、C等位基因频率在URSA组和对照组的分布无差异（P=0．18、0．08）。（4）单体型分析：del-A-G单体型明显增加URSA的发病风险（OR=2．51，P〈0．01），而del-C-G和A。r11-A-A单体型则对URSA的发病具有保护作用（OR=0．18、0．22，P均〈0．01）。结论Foxp3基因的功能性多态位点可能通过改变Foxp3基因的表达或其功能而增加URSA的发病风险。Objective To investigate the association between the functional polymorphisms of Foxp3gene and unexplained recurrent spontaneous abortion （ URSA）. Methods PCR-restriction fragment length polymorphism （rs3761548, rs2294021） and PCR with sequence-specific primers （rs2232365, rs5902434） were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. Results （ 1 ） The frequencies of rs3761548A/C were 10. 3% , 22. 3% in genotype C/C, 38.4% ,40. 2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50. 0% in genotype A/G, 46. 6%, 34. 8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference （P 〈0. 05）. The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA （OR = 1.73, 1.61 ;all P 〈0. 05）. （2） There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls （P = 0. 10 ）, but the frequency of del allele in URSA was statistically increased than that of controls （71.2%, 62. 5% ;OR = 1.49, P = 0. 04）. （3） There was no different distribution in 3 genotypes （C/C, T/C, T/T） and 2 alleles （T and C） of rs2294021T/C between URSA patients and normal controls （P = 0. 18 and 0. 08）. （4） Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA （OR = 2.51, P 〈 O. 01 ） but haplotype del-C-G and ATT-A-A could provide protection on URSA （ OR = 0. 18, 0. 22 ; all P 〈 0. 01 ）. Conclusion Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and （or） its expression.

关 键 词：流产 习惯性 叉头转录因子类 多态现象 遗传 T淋巴细胞 调节性 疾病 遗传易感性 

分 类 号：R714.21[医药卫生—妇产科学]