与宁夏人群强直性脊柱炎关联的新基因淋巴毒素-α(LTA)的识别

Identification of a novel lymphotoxin-alpha (LTA) gene associated with ankylosing spondylitis in Ningxia population

淋巴毒素-α(Lymphotoxin-alpha,LTA)基因与系统性红斑狼疮、银屑病及类风湿性关节炎的遗传性有关,但目前还未有关于LTA基因与强直性脊柱炎(Ankylosing spondylitis,AS)关联的报道。文章采用病例-对照设计,在宁夏人群中对人类白细胞抗原(Human leukocyte antigen,HLA)的Ⅲ类基因约58 kb区域进行了高密度标志的基因组扫描,在33个SNPs及其单倍型中,仅定位于LTA基因中的SNPs组成的TCC单倍型的分布在病例-对照间比较有统计学意义(P=0.0005)。在宁夏群体(病例组:300,对照组:385)中发现,LTA基因中的rs909253 T/C多态性在AS患者中出现的频率显著高于正常对照(28.5%vs 19.7%,P=2×10-6)。结果表明LTA基因变异和AS易感性之间存在相关性,由此识别LTA基因可能与宁夏人群AS关联。

Lymphotoxin-alpha （LTA） gene has been reported to have a genetic association with systemic lupus erythema- tosus （SLE）, psoriasis, and rheumatoid arthritis. However, the association of LTA with ankylosing spondylitis （AS） has not reported. By case-control study, we carried out the high density limited genome scanning to the HLA class III region about 58 kb in Ningxia population （case 300 and control 385）. In this study, 33 SNPs in LTA were genotyped in Ningxia popula- tion. We analyzed these SNPs and the haplotypes covering LTd. Only the distribution of TCC haplotype which contains mutation allele of LTA rs909253 was statistically significant（P-0.0005）. The C allele frequency of the LTA rs909253 TIC polymomhism was higher in AS cases than that in the controls （28.5% versus 19.7%, P=2×10-4） in Ningxia population. Theresults suggest that there is a relevance between LTA and the susceptibility of AS, and we identified that the LTA polymorphism may be associated with AS in Ningxia population.