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日本HLA - B27相关急性前葡萄膜炎患者的MICA基因多态性和HLA - B27亚型

MICA gene polymorphisms and HLA-B27 subtypes in Japanese patients with HLA-B27-associated acute anterior uveitis.

作者信息

Goto K, Ota M, Ando H, Mizuki N, Nakamura S, Inoue K, Yabuki K, Kotake S, Katsuyama Y, Kimura M, Inoko H, Ohno S

机构信息

Department of Ophthalmology, Yokohama City University School of Medicine, Japan.

出版信息

Invest Ophthalmol Vis Sci. 1998 Mar;39(3):634-7.

PMID:9501876
Abstract

PURPOSE

HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes.

METHODS

Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method.

RESULTS

The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls.

CONCLUSIONS

These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.

摘要

目的

HLA - B27相关性急性前葡萄膜炎(HLA - B27 AAU)似乎是由特定遗传背景的个体中的外部因素引发的。HLA - B27或HLA - B区域附近的其他基因是否通过与B27的连锁不平衡而使个体易患葡萄膜炎仍不确定。作者研究了位于HLA - B基因着丝粒侧47 kb处的MICA基因跨膜区域内的微卫星多态性以及HLA - B27亚型。

方法

采用聚合酶链反应(PCR)及随后基于荧光技术的自动片段检测,对17例HLA - B27阳性的日本HLA - B27 AAU患者、51例日本对照者以及20例B27阳性的日本对照者进行MICA基因跨膜区域内的多态性检测。此外,采用PCR - 序列特异性引物法对HLA - B27 AAU的B27阳性患者和B27阳性对照者进行HLA - B27亚型检测。

结果

MICA基因中的微卫星等位基因,由GCT/AGC的四个重复序列组成(命名为A4等位基因),在患者组中的表型频率(64.7%)显著高于对照组(25.5%)(χ2 = 6.95,Pc = 0.042)。此外,即使与B27阳性对照组的20%相比,A4等位基因的频率也显著更高(χ2 = 5.88,Pc = 0.042)。HLA - B27 AAU的B27阳性患者与B27阳性对照者之间HLA - B27亚型的频率无显著差异。

结论

这些结果表明,MICA基因本身或与MICA A4等位基因连锁的其他附近基因可能参与了HLA - B27 AAU的发病过程,并且在日本人群中,HLA - B27亚型在HLA - B27 AAU的发病中并不重要。

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