杀伤细胞免疫球蛋白样受体及其配体基因多态性与Graves病的相关性研究

Correlation between gene polymorphisms of killer cell immunoglobulin-like receptors and their ligands and Graves′ disease

目的探讨杀伤细胞免疫球蛋白样受体(KIR)与其配体特异性人类白细胞抗原C(HLA-C)的基因多态性与Graves病(GD)的相关性。方法病例对照研究。回顾性纳入2011年1月至2017年12月于山东省立医院就诊的118例无血缘关系的GD患者(GD组)以及同期108名年龄、性别相匹配的健康对照人群(健康对照组),采用聚合酶链反应序列特异性引物方法(PCR-SSP)对其KIR基因型及其配体HLA-C等位基因进行检测,并分析KIR/HLA-C基因组合在GD患者及对照人群中的分布情况,探讨其与GD发生的关联。结果GD组中,男29例,女89例,年龄(38±14)岁;健康对照组中,男28名,女80名,年龄(37±13)岁。与健康对照组相比,GD组的HLA-Cw01出现的频率较高[36.4%(43/118)比18.5%(20/108),P=0.003],HLA-Cw03和HLA-Cw06出现的频率较低[11.9%(14/118)比39.8%(43/108),P<0.001;9.3%(11/118)比18.5%(20/108),P=0.045]。KIR2DL1/HLA-C2基因组合在GD组中的频率低于对照组[17.8%(21/118)比34.3%(37/108),P=0.005]。logistic回归分析显示KIR2DL1/HLA-C2基因组合是GD发生的保护因素(OR=0.308,95%CI:0.126~0.752,P=0.010)。结论KIR/HLA-C基因多态性与GD有关,KIR2DL1/HLA-C2在GD患者中低表达,可能是GD发生的保护因素。

Objective To explore the relationship between gene polymorphism of killer cell immunoglobulin-like receptor(KIR)and its ligand-specific human leukocyte antigen C(HLA-C)and Graves′disease(GD).Methods Case-control study.A total of 118 unrelated GD patients(GD group)admitted to Shandong Provincial Hospital from January 2011 to December 2017 and 108 age-and sex-matched healthy controls(healthy control group)were included.The KIR genotype and its ligand HLA-C allele were detected by polymerase chain reaction sequence-specific primers(PCR-SSP).The distribution of KIR/HLA-C gene combination in GD patients and control population was analyzed to explore its association with the occurrence of GD.Results In GD group,there were 29 males and 89 females,aged(38±14)years.In the healthy control group,there were 28 males and 80 females,aged(37±13)years.Compared with the healthy control group,the occurrence frequency of HLA-Cw01 was higher in GD group[36.4%(43/118)vs 18.5%(20/108),P=0.003],and the occurrence frequency of HLA-Cw03 and HLA-Cw06 was lower in GD group[11.9%(14/118)vs 39.8%(43/108),P<0.001;9.3%(11/118)vs 18.5%(20/108),P=0.045].The frequency of KIR2DL1/HLA-C2 gene combination in GD group was lower than that in control group[17.8%(21/118)vs 34.3%(37/108),P=0.005].Logistic regression analysis showed that KIR2DL1/HLA-C2 gene combination was a protective factor for GD occurrence(OR=0.308,95%CI:0.126-0.752,P=0.010).Conclusions The polymorphism of KIR/HLA-C gene is related to GD.The low expression of KIR2DL1/HLA-C2 in GD patients may be a protective factor for GD.