HLA-A*2402 and a microsatellite (D6S248) are secondary independent susceptibility markers to ankylosing spondylitis in Basque patients
HLA-A*2402 and a microsatellite (D6S248) are secondary independent susceptibility markers to ankylosing spondylitis in Basque patients
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DOI：
10.1016/j.humimm.2003.11.006
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发表时间：
2004-02-01
期刊：
影响因子：
2.7
通讯作者：
Cuadrado, E
中科院分区：
文献类型：
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作者：
de Juan, MD;Reta, A;Cuadrado, E
强直性脊柱炎(AS)普遍与人类白细胞抗原B27(人类白细胞抗原B27)相关，尽管其他基因可以决定疾病的发展和临床表现。人类白细胞抗原-A9(A*2402)等位基因此前已被发现与巴斯克患者相关。本研究的目的是更精确地分析人类白细胞抗原-A*2402和B27单倍型的微卫星多态，以阐明这种关联的意义。对50例无血缘关系的强直性脊柱炎患者和113例巴斯克族对照进行了研究。分析与人类白细胞抗原-A和-B相邻的I类主要组织相容性复合体区域的8个微卫星，评估AS的等位基因关联强度和等位基因间的连锁不平衡(LD)。D6S248、1000Kb端粒基因D6S248的等位基因15与本病呈正相关(OR：6；p(C)=4.7×10(-4))，不能用LD与HLA1327、HLAA*2402或其他基因座相关联。我们发现D6S248-15等位基因与人类白细胞抗原-A*2402一起可能是巴斯克AS患者附加易感基因/S位于人类白细胞抗原-A端粒区域的B27非依赖性标记。
Ankylosing spondylitis (AS) is universally associated with human leukocyte antigen B27 (HLA-B27), although other genes could determine the development and clinical expression of the disease. HLA-A9 (A*2402) allele was previously found to be associated in Basque patients. The objective of this study is to perform a more precise analysis of microsatellite polymorphisms in HLA-A*2402 and B27 haplotypes to elucidate the significance of this association. A group of 50 unrelated AS patients and 113 controls of Basque origin were studied. Eight microsatellites in the class I major histocompatibility complex region with vicinity to HLA-A and -B were analyzed and the strength of allelic associations to AS and linkage disequilibriurn (LD) between alleles were evaluated. Allele 15 at the microsatellite locus D6S248, 1000Kb telomeric to HLA-A showed a strong positive association with the disease( OR:6; p(c) = 4.7 X 10(-4)) and it could not be explained by LD to HLA-1327, HLA-A*2402 or any other loci. We found that D6S248-15 allele together with HLA-A*2402 could be B27-independent markers of additional susceptibility gene/s localised in the region telomeric to HLA-A in Basque AS patients.