中国南方汉族急性淋巴细胞白血病患者572例的HLA基因和单倍型分析

Study on HLA alleles and haplotypes of 572 patients with acute lymphoblastic leukemia in southern Chinese Han

目的研究HLA—A、B、DRB1基因和单倍型与中国南方汉族急性淋巴细胞白血病（ALL）的疾病相关性。方法应用最大似然性方法分别计算南方汉族ALL患者组572例和5645名南方汉族健康供者HLA—A、B、DRB1基因和单倍型频率，采用X^2检验方法比较其分布差异。结果ALL组HLA—A33、B58和DRB1^＊17基因频率均低于对照组[HLA—A33（7．15％比93％，OR=0．73，P〈0．05）、B58（5．93％比8．75％，OR=0．64，P〈0．05）和DRB1^＊17（5．15％比6．30％，OR=0．82，P〈0．05）]；A3、B51和DRB^＊12基因频率均高于对照组[A3（2．1％比1．26％，OR=1．7，P〈0．05），B51（7．25％比5．78％，OR=1．3，P〈0．05）和DRB^＊12（16．13％比12．99％，OR=1．35，P〈0．05）]；HLA—A33-B58-DRB1^＊17单倍型频率低于对照组（2．46％比4．14％，OR=0．35，P〈0．05），A2-B51-DRB1^＊12单倍型频率高于对照组（1．24％比0．89％，OR=1．66，P〈0．05）。结论携带有A33-B58-DRB1^＊17单倍型个体可能与降低ALL的发病风险有相关性，A3基因和A2-B51-DRB1^＊12可能与增加ALL发病风险有弱相关性。

Objective To study the distributive characteristics of HLA-A, B, DRB1 alleles and haplotypes patients with ALL in southern Chinese Hun. Methods The frequencies of HLA-A, B, DRB1 alleles and haplotypes were estimated by Expectation-Maximization method based on the genotypes of 572 patients with ALL and 5645 unrelated health donors, and then compared by chi-square test. Results The frequencies of HLA-A33（7.15 % vs 9.3 %, OR=0.73, P 〈0.05）, B58（5.93 % vs 8.75 %, 0R=0.64, P 〈0.05）, DRB1^＊17（5.15 % vs 6.30 %, OR=0.82, P 〈0.05） alleles and HLA-A33-B58-DRB1^＊17（2.46 % vs 4.14 %, OR=0.35, P 〈0.05） haplotype were significantly lower in ALL patient groups than that in controls. The frequencies of HLA-A3（2.1% vs 1.26 %, OR=1.7, P 〈0.05）, B51 （7.25 % vs 5.78 %, OR=1.3, P 〈0.05） and DRB^＊12 （16.13 % vs 12.99 %, OR=1.35, P 〈0.05） alleles and A2-B51- DRB1^＊12（1.24 % vs. 0.89 %, OR= 1.66, P 〈0.05） haplotype were significantly higher in ALL patient groups than that in controls. Conclusion These results indicated that HLA-A33-B58-DRB1^＊17 baplotype was a associated with a diminished incidence of ALL, and HLA-A3 allele or A2-B51- DRB1^＊12 haplotype was weakly associated with ALL.