HLA-DQ等位基因多态性与反复种植失败的关系

The relationship between HLA-DQ allele polymorphism and recurrent implantation failure

目的探讨反复种植失败与夫妇双方HLA-DQ等位基因多态性之间的关系。方法选取44例反复种植失败(RIF组)的患者和16例(对照组)同期接受体外受精-胚胎移植且在第1周期成功妊娠的患者,采用序列特异性引物PCR和基因测序分型的方法分别检测夫妇双方HLA-DQA1和HLA-DQB1的基因位点,采用χ2检验和Fisher’s精确检验比较2组等位基因频率和相容性的差异。结果等位基因HLA-DQB1*03:01、HLA-DQB1*03:02、HLA-DQB1*03:03在RIF组中的出现频率高于对照组,但差异均无统计学意义(P>0.05);将以上3个位点合并为HLA-DQB1*03后,在女方RIF组中出现频率显著高于对照组(52.28%vs31.26%,P<0.05);而HLA-DQB1*05:02等位基因频率在RIF组中低于对照组(女:9.09%vs 12.50%,男:6.82%vs 21.88%),且在男方中差异有统计学意义(P<0.05)。HLA-DQA1等位基因位点频率分布在RIF组和对照组之间无统计学意义(P>0.05);HLA-DQ单元型、夫妇双方HLA-DQ的相容性与对照组相比差异均无统计学意义(P>0.05)。结论 HLA-DQ等位基因的多态性在反复种植失败中可能扮演重要的作用,HLA-DQB1*03可能是一个导致种植失败的易感基因,而HLA-DQB1*05:02可能是一个保护性基因。

To explore the relationship between human leukocyte antigen（HLA）-DQ allele polymorphism and recurrent implantation failure（RIF）,HLA-DQA1 and HLA-DQB1 genotyping was carried out by the polymerase chain reaction sequence specific primer（PCR-SSP） and sequence based typing（SBT） methods in 44 couples with RIF（RIF group） and 16 couples who were successful pregnancy in first IVF-ET cycle（control group）.The difference in HLA-DQ gene frequencies and sharing were analyzed by using chi-square test and Fisher＇s exact test.In RIF group,the frequencies of HLA-DQB1＊03：01,HLA-DQB1＊03：02 and HLA-DQB1＊03∶03 were higher than those in control group,but the differences were not statistically significant（P 0.05）;when merge the three alleles to become HLA-DQB1＊03,in females,the frequency was significant increased in RIF group compared to the control group（52.28% vs 31.26%,P 0.05）;but the frequency of HLA-DQB1＊05：02 was lower in RIF group compared to the control group（female： 9.09% vs 12.50%,male： 6.82% vs 21.88%） and statistically significant difference was existed in males（P 0.05）.The distribution of HLA-DQA1 alleles did not differ significantly between two groups（P 0.05）,furthermore,no significant difference was observed in HLA-DQ sharing and haplotype between the two groups（P 0.05）.The results suggest that HLA-DQB1 alleles might play an important role in RIF,DQB1＊03 allele may be a susceptible gene to RIF,and DQB1＊05：02 allele may be a protective gene to RIF.