Association of genetic polymorphisms of KIR-HLA system with chronic myeloid leukemia among ethnic Hans from southern China.
- VernacularTitle:南方汉族KIR-HLA系统基因多态性与慢性髓系白血病的相关性
- Author:
Zhihui DENG
1
;
Jianxin ZHEN
;
Daming WANG
;
Liumei HE
;
Hongyan ZOU
Author Information
- Publication Type:Journal Article
- MeSH: Asian Continental Ancestry Group; genetics; China; Gene Frequency; Genetic Predisposition to Disease; ethnology; genetics; Genotyping Techniques; HLA Antigens; genetics; HLA-A Antigens; genetics; HLA-B Antigens; genetics; HLA-C Antigens; genetics; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; ethnology; genetics; Odds Ratio; Polymerase Chain Reaction; Polymorphism, Genetic; Protein Isoforms; genetics; Receptors, KIR; genetics; Risk Factors
- From: Chinese Journal of Medical Genetics 2017;34(1):53-57
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the association of KIR-HLA gene polymorphism with chronic myeloid leukemia (CML) among ethnic Hans from southern China.
METHODSA total of 172 adult CML patients and 480 unrelated healthy controls were screened for the presence of KIR with sequence-specific primers-PCR (PCR-SSP) and sequence-based typing (SBT) of HLA-A, -B and -C loci. Polymorphisms of the KIR-HLA system were analyzed at 4 levels, and the frequencies of KIR framework genes and KIR profiles, classⅠHLA ligands, matched KIR+HLA pairs and KIR-HLA compound profile were compared between the two groups. P values were calculated using SPSS 13.0 software.
RESULTSFor the CML group, the frequencies of HLA-C2 ligand, 2DL1+HLA-C2 pair and HLA-B Bw4-80I were significantly lower than those of the control group, suggesting a protective effect against CML (HLA-C2: OR=0.386, 95%CI:0.240-0.620, P<0.01; 2DL1+HLA-C2: OR=0.316, 95%CI:0.191-0.525, P<0.01; HLA-B Bw4-80I: OR=0.576, 95%CI:0.384-0.862, P<0.01). The frequencies of KIR2DL1 ligand (HLA-C2) and KIR3DL1 ligand (HLA-B Bw4-80I) in the CML group were significantly lower than that of the control group, suggesting that the HLA-C2 and HLA-B Bw4-80I expression is probably decreased in the CML patient group, which led to reduced inhibitory signal and enhanced activating signal of KIR2DL1and/or KIR3DL1NK cells. Notably, the frequency of KIR-HLA compound profiles ID2 (KIR AA1-HLA-C1/C1-Bw6/Bw6-A3/11) in CML patients significantly increased in the CML patient group compared with the control group, suggesting that the KIR-HLA compound profiles ID2 may be a risk factor for CML (OR=2.163, 95%CI 1.198-3.906, P<0.01).
CONCLUSIONAbove analysis has identified certain protective and risk factors for CML from the KIR-HLA system, which may provide a clue for the pathogenesis of leukemia and development of individualized immune therapy.
