日本扩张型心肌病患者 HLA Ⅱ类基因的 DNA 分型

DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy.

作者信息

Nishi H, Koga Y, Koyanagi T, Harada H, Imaizumi T, Toshima H, Sasazuki T, Kimura A

机构信息

Department of Genetics, Kyushu University, Fukuoka, Japan.

出版信息

J Mol Cell Cardiol. 1995 Oct;27(10):2385-92. doi: 10.1016/s0022-2828(95)92091-9.

DOI:10.1016/s0022-2828(95)92091-9

PMID:8576952

Abstract

HLA class II genes (DRB, DQA, DQB, DPA, and DPB) were typed at the DNA level using polymerase chain reaction/sequence-specific oligonucleotide probe analysis in 78 unrelated patients with DCM and 336 unrelated healthy controls to elucidate the HLA alleles or HLA haplotypes associated with DCM. The frequencies of DRB11401 (15.4% v 4.5%, RR = 3.90, P < 0.0005, Pc < 0.03), DQB10503 (14.1% v 5.4%, RR = 2.93, P < 0.007) and DRB11401-DQB10503 haplotype (11.5% v 1.5%, RR = 8.24, P < 0.00001, Pc < 0.01) were increased in the DCM patients. The frequency of HLA-DRB11101 (9.0% v 3.0%, RR = 3.26, P < 0.02) also was increased in the patients. In addition, the frequencies of DQB10604 and DPB10401 were increased in the DRB11401 and DRB11101 negative patients. In contrast, the frequencies of DQB10303 (19.2% v 30.7%, RR = 0.55, P < 0.05) and DRB10901-DQB10303 haplotype (16.7% v 29.8%, RR = 0.49, P < 0.02) were decreased in the DCM group. Disease susceptibility to DCM in the Japanese population, thus, may be controlled in part by a gene (or genes) in close linkage disequilibrium with DRB11401-DQB10503, DRB11101-DQB10301, and DQB10604-DPB10401 haplotypes, while the resistance to DCM may be associated with the DRB10901-DQB10303 haplotype.

摘要

采用聚合酶链反应/序列特异性寡核苷酸探针分析法，在DNA水平对78例非亲缘关系的扩张型心肌病（DCM）患者及336例非亲缘关系的健康对照者进行HLAⅡ类基因（DRB、DQA、DQB、DPA和DPB）分型，以阐明与DCM相关的HLA等位基因或HLA单倍型。DCM患者中DRB11401（15.4%对4.5%，相对危险度RR = 3.90，P < 0.0005，校正P值Pc < 0.03）、DQB10503（14.1%对5.4%，RR = 2.93，P < 0.007）以及DRB11401 - DQB10503单倍型（11.5%对1.5%，RR = 8.24，P < 0.00001，Pc < 0.01）的频率升高。患者中HLA - DRB11101的频率（9.0%对3.0%，RR = 3.26，P < 0.02）也升高。此外，在DRB11401和DRB11101阴性的患者中，DQB10604和DPB10401的频率升高。相反，DCM组中DQB10303（19.2%对30.7%，RR = 0.55，P < 0.05）以及DRB10901 - DQB10303单倍型（16.7%对29.8%，RR = 0.49，P < 0.02）的频率降低。因此,日本人群中DCM的疾病易感性可能部分受与DRB11401 - DQB10503、DRB11101 - DQB10301和DQB10604 - DPB10401单倍型紧密连锁不平衡的一个或多个基因控制，而对DCM的抵抗力可能与DRB10901 - DQB10303单倍型有关。