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

目的探讨皖籍汉族人群MICA基因（major histocompatibility complex class Ⅰchain-related gene A，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（ankylosing spondylitis，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（polymerase chain reactionsequence-specific oligonucleotide probing，PCR-SS0）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（X^2=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（X^2=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。

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

OBJECTIVE: To investigate the association between the exons 2 to 4 of the MICA gene and ankylosing 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. RESULTS: 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 (chi-square=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 difference in MICA*007-B27 between two groups (chi-square=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.