Relationship between High-Resolution HLA-A,-B,-DRB1 Alleles and Haplotype Polymorphisms with Myeloid Leukemia of Han People in North China / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the potential relationship between the high-resolution HLA-A,-B,-DRB1 alleles and haplotype polymorphism with actute myeloid leukemia (AML) and chronic myeloid leukemia (CML) of Han people in North China.</p><p><b>METHODS</b>A total of 1241 healthy unrelated Han people's bone marrow donors in North China were used as a control group, 259 patients with myeloid leukemia were genotyped at high-resolution level by means of PCR-SBT, -SSO and -SSP typing methods for HLA-A,-B,-DRB1 loci. The frequencies of HLA allele and haplotype were calculated by software Arleguin 3.5.2. The different distribution of genes and haplotypes was analyzed by case control study, and the odd ratio (OR) of leukemia was also calculated. The structural difference of HLA alleles was analyzed 111by HLA three-dimensional structure modeling and software Swiss-PdbViewer v4.1.</p><p><b>RESULTS</b>χtest and correction showed that an increased frequency of A*0207 (8.47% vs 5.28%, P' =0.013), A*2901 (1.85% vs 0.68%, P=0.044), B*0702 (5.29% vs 3.10%, P=0.029), B*070501G (1.85% vs 0.68%, P=0.044) and B*3502 (1.06% vs 0.20%, P=0.023) were found in AML patients (n=189) as compared with controls, respectively; whereas A*0203 was less frequent in AML as compared with controls (0.79% vs 3.10%, P=0.011). The frequency of B*4601 was lower in CML patients (n=70) as compared with controls (2.86% vs 7.82%, P=0.031). However, the above-mentioned discrepancies were not statistically significant by Bonferroni correction. Through Fisher exact test and Bonferroni correction, the frequency of DRB1*1128 and its haplotype A*2402-B*1501-DRB1*1128 in CML group were very significantly higher than in controls (1.43% vs 0.00%, Pc=0.015; 1.43% vs 0.00%, P=0.003). Three-dimensional structure modeling of DRB1*1128 and DRB1*1101 presented significant structure differentiation (RMSD=0.09 nm) in peptide binding region of the backbone calculated by Swiss-PdbViewer v4.1. The haplotype A*0301-B*5001-DRB1*0701 in AML and A*1101-B*4006-DRB1*0901 in CML patients were significantly higher than that in controls (1.06% vs 0.00%, Pc=0.000; 2.86% vs 0.07%, Pc=0.000), and positively correlated with leukemia (OR=59.66, 95% CI=3.21-1110.39; OR=42.91, 95% CI=7.07-260.32).</p><p><b>CONCLUSION</b>The relationship of HLA-A,-B,-DRB1 alleles and haplotype polymorphism with leukemia at high-resolution level were obtained and unique in north Chinese Han population. AML and CML patients in Northern Han people carry particular susceptible haplotypes. DRB1*1128, which might not actively present bcr-abl peptide to CD4T cells, and is a susceptibile gene for CML patients of Northern Han people, especially in Shaanxi Province (OR=89.62, 95% CI=4.28-1875.87), as well as correlated with its particular haplotype.</p>