强直性脊柱炎患者MICA基因第2、3和4外显子的多态性及其与HLA-B抗原的连锁不平衡

Disequilibrium linkage between the polymorphism in exons 2,3 and 4 of the MICA gene and HLA-B antigen of patient with ankylosing spondylitis

目的探讨皖籍汉族人群MICA基因(majorhistocompatibilitycomplexclassⅠchain-relatedgeneA,MICA)第2、3、4外显子的多态性,及其与HLA-B抗原的连锁不平衡在强直性脊柱炎(ankylosingspondylitis,AS)发病中的作用。方法采用聚合酶链反应-序列特异性寡核苷酸探针杂交(polymerasechainreaction-sequence-specificoligonucleotideprobing,PCR-SSO)技术对56例AS患者和112名正常对照人群进行MICA基因第2、3、4外显子的多态性和HLA-B抗原的检测。结果AS患者和正常对照人群的MICA等位基因分布均以MICA*008占优势,频率分别为32.14%和30.36%。两组人群MICA*007等位基因的分布差异有统计学意义(χ2=10.18,P<0.05,RR=2.50)。单倍型分析显示,AS患者和正常对照人群的MICA等位基因均显示出与多个HLA-B位点的连锁不平衡现象,两组间差异有统计学意义的单倍型为MICA*007-B27(χ2=18·46,P<0.05,RR=7.47)。分层分析结果显示,HLA-B27阳性与AS的相关性有统计学意义(P<0·05),但MICA*007基因与AS的相关性无统计学意义(P>0.05)。结论AS患者中MICA*007等位基因频率的显著升高可能源于MICA基因与HLA-B位点间的广泛连锁不平衡。

Objective To investigate the association between the exons 2 to 4 of the MICA gene and ankylesing spondylitis （AS）. Methods By PCR-SSOP, DNA samples from 56 AS patients and 112 random healthy individuals, as normal control were genotyped to analyse the polymorphism in exons 2,3,4 of the MICA alleles. Resets MICA ＊ 008 was dominant in MICA allele,accounted for 32.14% and 30.36% in AS patients and normal controls respectively. The frequency of MICA ＊ 007 was significantly increased in AS patients,when compared with normal controls （X^2 = 10.18, P 〈 0.05,RR= 2.50）. No difference was found in the other MICA alleles. The haplotype analysis revealed that there were the strong linkage disequilibrium between MICA and HLA-B of AS patients, and normal controls. There was a different in MICA ＊ 007-B27 between two groups（X^2 = 18.46, P 〈 0.05,RR = 7.47）. Both HLA-B27 and MICA ＊ 007 were strongly associated with AS. Stratified analysis showed that HLA-B27 was significantly relative to AS, while it was not found between MICA ＊ 007 and AS. Conclusion The increased frequency of MICA alleles may be due to its strong linkage disequilibrium with HLA-B27.