HLA-A、-B、-DRB1等位基因多态性与儿童获得性再生障碍性贫血的易感相关性研究  

Relationship between Polymorphism of HLA-A,-B,-DRB1 Alleles and Susceptibility of Children to Acquired Aplastic Anemia

作　　者：路素英[1,2] 肖露露[3] 罗敏[3] 张碧红[4] 陈纯[4] 

机构地区：[1]中山大学肿瘤防治中心儿童肿瘤科,广东广州510060 [2]华南肿瘤学国家重点实验室,广东广州510060 [3]南方医科大学南方医院器官移植科,广东广州510515 [4]中山大学孙逸仙纪念医院儿科,广东广州510120

出　　处：《中国实验血液学杂志》2012年第1期120-124,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号30772367);广东省自然基金自由申请项目(编号8151008901000099);广东省科技计划项目(编号2008B030301066)资助

摘　　要：本研究探讨儿童再生障碍性贫血(AA)易感与HLA-A、-B、-DRB1等位基因多态性之间的相关性。获得性AA患儿80例,其中男48例、女32例,平均年龄8.1岁。在80例AA患者中非重型AA(nsAA)6例,重型AA(sAA)74例。同地区随机选择健康献血者109例作为对照。采用PCR-SSP方法进行HLA-A、-B、-DRB1高分辨等位基因分型。基因频率差异分析采用Pearsonχ2检验或连续性校正χ2检验或Fisher精确概率法。结果表明,与健康对照组比较,80例AA儿童患者中,HLA-B*48:01、DRB1*09:01表达频率升高(均P<0.05,OR分别为12.000和3.403);HLA-B*51:01、DRB1*03:01、DRB1*11:01表达频率降低(均P<0.05,OR分别为0.207、0.266和0.139)。研究还发现,在74例SAA患儿中HLA-B*48:01、DRB1*09:01的表达频率与健康对照组相比亦呈显著升高,而HLA-B*51:01、DRB1*03:01、DRB1*11:01的表达频率与健康对照组相比均显著降低。结论:HLA-B*48:01、DRB1*09:01与儿童期AA相关联,可能是罹患儿童期SAA的易感风险基因。HLA-B*51:01、DRB1*03:01、DRB1*11:01在儿童AA中低表达,是否为相对的保护基因有待进一步研究。The aim of this study was to identify the relationship between susceptibility of children to acquired aplastic anemia（AA） and HI.A-A, -B, -DRB1 alleles. 80 children with AA were enrolled in this study. Among of them, 34 patients collected from tissue typing test centers of Nanfang Hospital; 46 patients were diagnosed at Department of Pediatrics of Sun Yat-Sen Memorial Hospital. In these patients, 48 were males, 32 were females, and with average age 8.1 years old, 6 cases were non-severe AA （nSAA） , 74 case were severe AA （SAA）. The healthy control group consisted of 109 donors who were from the same area. All the patients and healthy controls were of Han Chinese, and all were unrelated individuals. The polymerase chain reaction sequence specific primers （PCR-SSP） was used to analyze the polymorphism of HLA-A, -B and -DRB1 alleles. Pearson Chi-square or continuity correction or two-sided Fisher＇s exact test were used. The results showed that the genotype frequency of HLA-B ＊ 48：01 and DRB1 ＊ 09：01 were significantly higher in children with AA as compared with healthy controls （ P 〈 0.05 ）. The genotype frequency of HLA-B ＊ 51 ： 01, DRB1 ~ 03：01 and DRB1 ＊ 11：01 were significantly lower in children with AA as compared with healthy controls（P 〈 0. 05 ）. Besides, the results also demonstrated that the genotype frequencies of HLA-B ＊ 48：01 and DRB1 ＊ 09：01 were significantly higher in SAA as compared with controls, the genotype frequencies of B＊ 51：01, DRB1＊ 03：01 and DRB1 v11：01 were significantly lower in SAA, as compared with controls. In conclusion, HLA-B ＊48：01 and DRB1 ＊ 09：01are related with children AA, and may be susceptible alleles to the development of children AA. Besides, the expression of HLA-B ＊ 51：01, DRB1 ＊ 03：01 and DRB1 ＊ 11：01 are low in children with AA, whether they are relative protection alleles of children needs to be further studied.

关 键 词：获得性再生障碍性贫血 HLA-A HLA-B HLA-DRB1 

分 类 号：R556.5[医药卫生—血液循环系统疾病]