中国汉族强直性脊柱炎患者人类白细胞抗原-B27多态性研究

Polymorphism of HLA-B27 in ankylosing spondylitis of Chinese Han population： B ＊ 2715 a noteworthy subtype

目的 本研究拟利用最新的人类白细胞抗原（HLA）-B27亚型数据，调查中国汉族强直性脊柱炎（AS）患者HLA—B27及其亚型的分布情况。方法从我院脊柱关节炎患者数据库中随机抽取100例AS患者。用luminex液态芯片，结合聚合酶链反应-序列特异性寡核苷酸探针（PCR～SSOP）技术对HLA—B位点作低分辨分型。HLA—B27阳性者进一步用聚合酶链反应-序列特异性引物（PCR—SSP）法做高分辨HLA—B27亚型检测。结果经随机抽样纳入无关AS患者98例，其中HLA—B27阳性93例，阳性率94．9％，其中B＊2704亚型76例（81．7％），B＊2705亚型12例（12．9％），B＊2715亚型5例（5．4％）。与另外2篇文献报道的HLA—B27阳性汉族健康人群比较，没有一致的证据表明HLA—B27亚型分布在AS患者和健康人群中存在差异。但这2项汉族健康人群中的研究均未发现BS2715亚型。结论中国汉族AS患者B27亚型以BS2704为主，其次是BS2705。BS2715作为一个频率极低的等位基因，本组病例中发现5例，提示B＊2715与AS发病存在关联。

Objective To investigate the distribution of HLA-B27 subtypes in ankylosing spondylitis （AS） patients of Chinese Han population by using the updated HLA-B27 typing data. Methods One hundred AS subjects were randomly selected from spondyloarthritis patients data bank of the third affiliated hospital of Sun Yat-sen university. All subjects were independent individuals, and the duplicated samples in the same family were excluded. Salt fraction method was used to prepare genome DNA. Luminex liquid array combining PCR-SSOP was used to perform the low resolution HLA-B genotyping. PCR-SSP was applied to perform the high resolution HLA-B27 typing for HLA-B27 positive subjects. Results Ninety-eight independent AS patients were recruited randomily, of which, 93 were HLA-B27 positive, with positive rate 94.9%, and covered 96% patients with family history of AS. Three subtypes were detected in this population including B ＊ 2704 （n=76, 81.7%）, B ＊ 2705 （n=12, 12.9%） and B ＊ 2715 （n=5, 5.4%）. Compared with the two reports about HLA-B27 subtype distribution in healthy HLA-B27 positive Han population there was no significant difference between AS patients and healthy controls. But no B ＊ 2715 case was found in those two reports of healthy population. Three reports （including 1 report in Chinese） could found about B ＊ 2715 subtype, but all positive cases were oriental people. Furthermore, all B ＊ 2715 positive patients were AS patients. Conclusion B ＊ 2704 is the predominant subtype in AS patients of Chinese Han population, and followed by B ＊ 2705. We found five cases with positive B ＊ 27i5, a considerable rare allele. This may suggest association between B ＊ 2715 and AS.