
幼年特发性关节炎患儿HLA-DRB1基因多态性分析
HLA-DRB1 allelic polymorphism in children with juvenile idiopathic arthritis
目的:研究广东地区汉族幼年特发性关节炎(JIA)患儿HLA-DRB1位点等位基因多态性分布特点。方法:采用序列特异性引物-聚合酶链反应(SSP-PCR)技术对94例JIA患儿和226例健康儿童HLA-DRB1的13个等位基因进行分析,并分析上述基因在各组中的分布。结果:JIA患儿HLA-DRB1*08(P=0.0014,OR=2.26)的分布频率明显高于健康儿童,HLA-DRB1*12(P=0.032,OR=0.55)的分布频率明显低于健康儿童。在JIA全身型及多关节型中HLA-DRB1*08明显增高,而HLA-DRB1*15在JIA全身型及少关节型中明显降低,观察组与对照组比较P<0.05,差异有统计学意义,其他各位点差异无统计学意义。结论: HLA-DRB1*08可能是JIA小儿的易感基因。HLA-DRB1*12可能是JIA小儿的保护基因,其中HLA-DRB1*08是全身型及多关节型的易感基因,而HLA-DRB1*15与全身型及少关节型保护基因密切相关。[中国当代儿科杂志,2010,12(5):333-337]
OBJECTIVE: To investigate the predisposing alleles of HLA-DRB1 genes in Han children with juvenile idiopathic arthritis (JIA) from Guangdong Province, China. METHODS: Polymerase chain reaction-specific sequence primers (PCR-SSP) method was used to type HLA-DRB1 subregions in 94 Han children with JIA and 226 Han healthy controls. RESULTS: The frequency of HLA-DRB1*08 allele in the JIA group was significantly higher than that in the control group (P=0.0014, OR=2.26), in contrast, the frequency of HLA-DRB1*12 allele was significantly lower than that in the control group (P=0.032, OR=0.55). It was found that in children with So-JIA subset (P=0.023, OR=2.25) and polyarthritis JIA subset (P=0.034, OR=2.81), the allele HLA-DRB1*08 was expressed most commonly. The allele HLA-DRB1*15 was expressed in a lower frequency in children with So-JIA subset (P=0.049, OR=0.413) and oligoarthritis subset (P=0.045, OR=0.16) compared with that in the control group. CONCLUSIONS: HLA-DRB1*08 may be the susceptible allele of JIA, while HLA-DRB1*12 may be the protective allele of JIA in Han children from Guangdong Province. HLA-DRB1*08 is the susceptible allele of So-JIA and polyarthrits. HLA-DRB1*15 is the protective allele for systemic JIA and oligoarthritis.[Chin J Contemp Pediatr, 2010, 12 (5):333-337]
幼年特发性关节炎 / HLA-DRB1 / PCR-SSP / 儿童
Juvenile idiopathic arthritis / HLA-DRB1 / PCR-SSP / Isoform / Child
[1]Zeggini E, Packham J, Donn R, Wordsworth P, Hall A, Thomson W. Association of HLA-DRB1*13 with susceptibility to uveitis in juvenile idiopathic arthritis in two independent data sets[J]. Rheumatology (Oxford), 2006, 45(8):972-974.
[2]Prahalad S. Genetic analysis of juvenile rheumatoid arthritis:approaches to complex traits[J]. Curr Probl Pediatr Adolesc HealthCare, 2006, 36(3):83-90.
[3]Thomson W, Barrett JH, Donn R, Pepper L, Kennedy LJ, Ollier WE, et al. Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients[J]. Rheumatology (Oxford), 2002, 41(10):1183-1189.
[4]Zeggini E, Thomson W, Kwiatkowski D, Richardson A,Ollier W, Donn R, et al. Linkage and association studies of single nucleotide polymorphism-tagged tumour necrosis factor haplotypes in juvenile oligoarthritis[J]. Arthritis Rheum, 2002, 46(12):3304-3311.
[5]Zeggini E, Donn RP, Ollier WE, Thomson W; British Paediatric Rheumatology Study Group. Evidence for linkage of HLA loci in juvenile idiopathic oligoarthritis: independent effects of HLA-A and HLA-DRB1[J]. Arthritis Rheum, 2002, 46(10):2716-2720.
[6]Rubio JP, Bahlo M, Butzkueven H, van Der Mei IA, Sale MM, Dickinson JL, et al. Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis[J]. Am J Hum Genet, 2002, 70(5):1125-1137.
[7]Phelan JD, Thompson SD, Glass DN. Susceptibility to JRA/JIA:complementing general autoimmune and arthritis traits[J].Genes Immun, 2006, 7(1):1-10.
[8]Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001[J]. J Rheumatol, 2004, 31(2):390-392.
[9]Weiss JE, Ilowite NT. Juvenile idiopathic arthritis[J].Pediatr Clin North Am, 2005, 52(2):413-442.
[10]Olgerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence specific primers(PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor recipient matching in cadaveric transplantation[J].Tissue Antigens, 1992, 39(5):225-223.
[11]Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, et al. Nomenclature for factors of the HLA system , 2002[J].Hum Immunol, 2002, 63(12):1213-1268.
[12]Schreuder GM, Hurley CK, Marsh SG, Lau M, Fernandez-Vina MA, Noreen HJ, et al. HLA dictionary 2004: summary of HLA-A, -B, -C, DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens[J]. Hum Immunol, 2005, 66(2): 170-210.
[13]Prahalad S, Glass DN. A comprehensive review of the genetics of juvenile idiopathic arthritis[J]. Pediatr Rheumatol Online J, 2008, 6:11.
[14]Malysheva O, Pierer M, Wagner U, Wahle M, Wagner U, Baerwald CG: Association between beta 2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope[J]. Ann Rheum Dis 2008, 67(12): 1759-1764.
[15]余元勋,何光远,余国斌. 中国疾病相关基因与基因诊断[M].合肥:安徽科学技术出版社.第2版.2007:282-287.
[16]Saila H, Pitkaniemi J, Tuomilehto J, Savolainen N,Alakulppi N,Tuomilehto-Wolf E, et al. HLA and susceptibility to juvenile idiopathic arthritis: a study of affected sibpairs in an isolated Finnish population[J]. J Rheumatol, 2004, 31(11):2281-2285.
[17]Flato B, Hoffmann-Vold AM, Reiff A, Forre O, Lien G, Vinje O. Long-term outcome and prognostic factors in enthesitis-related arthritis[J]. Arthritis Rheum, 2006, 54(11):3573-3582.
[18]Thomson W, Barrett JH, Donn R, Pepper L, Kennedy LJ, Ollier WE, et al. Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients[J]. Rheumatology (Oxford), 2002, 41(10):1183-1189.