研究报告

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

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  • 1. 卫生部北京医院, 卫生部北京老年医学研究所, 北京100730 2. 宁夏医科大学医学遗传与细胞生物学教研室, 银川750004 3. 宁夏医科大学附属医院医学实验中心, 银川750004

收稿日期: 2010-07-26

  修回日期: 2010-08-23

  网络出版日期: 2011-04-25

基金资助

国家自然科学基金项目(编号:30972709, 81061120527)资助

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

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  • 1. Institute of Geriatrics, Beijing Hospital, Ministry of Health of PR China, Beijing 100730, China 2. Department of Cell Biology and Medical Genetics, Ningxia Medical University, Yinchuan 750004, China 3. Center of Medical Experiment, Affiliated Hospital of Ningxia Medical University, Yinchuan 750004, China

Received date: 2010-07-26

  Revised date: 2010-08-23

  Online published: 2011-04-25

摘要

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。

本文引用格式

陈静,周林,霍正浩,张毓洪,杨芝红,杨宝珍,黄慈波,朱小泉,杨泽 . 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[J]. 遗传, 2011 , 33(4) : 329 -336 . DOI: 10.3724/SP.J.1005.2011.00329

Abstract

Lymphotoxin-alpha (LTA) gene has been reported to have a genetic association with systemic lupus erythematosus (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 population. We analyzed these SNPs and the haplotypes covering LTA. 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 T/C polymorphism was higher in AS cases than that in the controls (28.5% versus 19.7%, P=2×10-4) in Ningxia population. The results 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.

参考文献

[1] Reveille JD, Sims AM, Danoy P, Evans DM, Leo P, Pointon JJ, Jin R, Zhou X, Bradbury LA, Appleton LH, Davis JC, Diekman L, Doan T, Dowling A, Brown MA. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet, 2010, 42(2): 123-127.
[2] Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum, 1998, 41(1): 58-67.
[3] Zhernakova A, van Diemen CC, WiJmenga C. Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat Rev Genet, 2009, 10(1): 43-55.
[4] 顾鸣敏, 袁文涛, 杨珏琴, 张静, 熊晓燕, 姚芳娟, 陆振虞, 王铸钢, 黄薇, 范丽安. 全基因组扫描寻找强直性脊柱炎的易感基因位点. 遗传学报, 2004, 31(3): 217-220.
[5] Brown MA, Pile KD, Kennedy LG, Campbell D, Andrew L, March R, Shatford JL, Weeks DE, Calin A, Words-worth BP. A genome-wide screen for susceptibility loci in ankylosing spondylitis. Arthritis Rheum, 1998, 41(4): 588-595.
[6] Laval SH, Timms A, Edwards S, Bradbury L, Brophy S, Milicic A, Rubin L, Siminovitch KA, Weeks DE, Calin A, Wordsworth BP, Brown MA. Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic- susceptibility loci. Am J Hum Genet, 2001, 68(4): 918-926.
[7] Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PIW, Maller J, Pe'er I, Burtt NP, Blumenstiel B, DeFelice M, Parkin M, Barry R, Winslow W, Altshuler D. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet, 2007, 39(12): 1477-1482.
[8] Burton PR, Clayton DG, Cardon LR, Craddock N, Delou-kas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Walker NM. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet, 2007, 39(11): 1329-1337.
[9] Karason A, Gudjonsso JE, Upmanyu R, Antonsdottir AA, Hauksson VB, Runasdottir EH, Jonsson HH, Gudbjartsson DF, Frigge ML, Kong A, Stefansson K, Valdimarsson H, Gulcher JR.A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting. Am J Hum Genet, 2003, 72(1): 125-131.
[10] 王雅文, 朱小泉, 宋玉国, 孙亮, 杨泽. 吉林人群强直性脊柱炎6号染色体短臂上的HLA区域遗传易感基因定位研究. 遗传, 2007, 29(7): 805-812.
[11] Goie The HS, Steven MM, van der Linden SM, Cats A. Evaluation of diagnostic criteria for ankylosing spondy-litis: A comparison of the Rome, New York and modified New York criteria in patients with a positive clinical his-tory screening test for ankylosing spondylitis. Br J Rheumatol, 1985, 24(3): 242-249.
[12] Calin A, Marder A, Becks E, Burns T. Genetic differences between B27 positive patients with ankylosing spondylitis and B27 positive healthy controls. Arthritis Rheum, 1983, 26(12): 1460-1464.
[13] van der Linden S, Valkenburg H, Cats A. The risk of developing ankylosing spondylitis in HLA-B27 positive in-dividuals: a family and population study. Br J Rheumatol, 1983, 22(4): 18-19.
[14] Paul NL, Ruddle NH. Lymphotoxin. Annu Rev Immunol, 1988, 6(4): 407-438.
[15] Banks TA, Rickert S, Ware CF. Restoring immune defenses via lymphotoxin signaling: lessons from cy-tomegalovirus. Immunol Res, 2006, 34(3): 243-254.
[16] Trabetti E, Patuzzo C, Malerba G, Galavotti R, Martinati LC, Boner AL, Pignatti PF. Association of a lymphotoxin alpha gene polymorphism and atopy in Italian families. J Med Genet, 1999, 36(4): 323-325.
[17] Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M, Migita T, Ito S, Ichikawa K, Matsui A, Arinami T. Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan. Clin Exp Allergy, 2005, 35(6): 790-796.
[18] Balding J, Kane D, Livingstone W, Mynett-Johnson L, Bresnihan B, Smith O, FitzGerald O.
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