中国北方汉族人群人类白细胞抗原-DQA1及-DQB1基因第二外显子多态性与扩张型心肌病遗传易感性研究

Polymorphism of the Second Exon of HLA-DQA1, -DQB1 Gene and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in the Hans of North China

目的:研究人类白细胞抗原(human leukocyte antigen,HLA)-DQA1,HLA-DQB1基因第二外显子多态性与我国北方汉族人群特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDC)的相关性及连锁关系。探讨特发性扩张型心肌病发病的免疫学机制及遗传易感性。 方法:采用聚合酶链反应-序列特异性引物法对68例特发性扩张型心肌病患者和15例特发性扩张型心肌病家系成员(n=83,IDC组)及100名健康个体(正常对照组)行HLA-DQA1,HLA-DQB1第二外显子基因分型;IDC组均接受超声心动图检测射血分数并据此分层:射血分数0.35-0.5者(n=21),射血分数0.15-0.34者(n=36)及<0.15者(n=26)。 结果:HLA-DQA1*0501基因和HLA-DQB1*0303基因频率在IDC组明显高于正常对照组。且该趋势随射血分数降低而愈趋明显,表现为HLA-DQA1*0501及HLA-DQB1*0303基因型在射血分数<0.15(阳性基因数分别为41和21)的特发性扩张型心肌病患者中分布高于射血分数≥0.15(阳性基因数分别为27和15)者。IDC组HLA-DQA1*0201基因频率和HLA-DQB1*0502、*0504基因频率明显低于正常对照组(P<0.05)。HLA-DQA1,HLA-DQB1基因与特发性扩张型心肌病家系连锁分析Lod值<1。 结论:HLA-DQA1*0501和HLA-DQB1*0303与我国北方汉族特发性扩张型心肌病患者遗传易感性相关;而HLA-DQA1*

Objective: To investigate the relationship between human leukocyte antigen (HLA)-DQA1, -DQB1 alleles second exon polymorphisms and susceptibility to idiopathic dilated cardiomyopathy (IDC) in the people of north China, and to explore the immu-nological mechanism and hereditary susceptibility to IDC.Methods: Polymerase chain reaction sequence-specific primer (PCR-SSP) techniques were used to analyze the polymorphisms of the second exon of HLA-DQA1 and HLA-DQB1 alleles in 68 unrelated IDC patients, 15 probands of IDC pedigrees, and 100 healthy controls.Results: The frequencies of HLA-DQA1 * 0501 and HLA-DQB1 * 0303 were 0. 4096 and 0. 2169 in the IDC group, significantly higher than those of the healthy controls (0.0900 and 0.0364, both p<0.05). The OR was 5. 34(95% CI:3. 61-7. 95) and 4. 92 (95% CI:2. 58-9. 01) , respectively. Further analysis of the three subgroups showed higher frequencies of HLA-DQA1 *0501 and HLA-DQB1 * 0303 in patients with EF <0. 15 than those with EF≥0. 15. Conversely, the frequencies of HLA-DQA1 * 0201 and HLA-DQB1 * 0502, * 0504 were significantly higher in the control group (0. 2000, 0. 0727 and 0. 1091) than in IDC group (0. 0241, 0. 0120 and 0. 0422) (the X2 values were 14. 55, 10. 68 and 9. 86, p<0. 05).Conclusion: The alleles of HLA-DQA1 * 0501 and HLA-DQB1 * 0303 confer susceptibility to IDC while DQA1 * 0201 and DQB1 * 0502, * 0504 alleles confer protection of IDC in the Han people of north China. The Serine(SER57) in the exon of DQB1* 0502 and * 0504 may be resistant to IDC. Any defect or substitute of this amino acid residue at position 57 of DQβ chain may be susceptible to IDC.