湖北地区肾综合征出血热与HLA—DRB基因多态性关联的研究

Association of hemorrhagic fever with renal syndrome and HLA-DRB allele polymorphisms in Han nationality, Hubei province

目的探索湖北省汉族人白细胞抗原（HLA）-DRB基因多态性与。肾综合征出血热（HFRS）的相关性。方法采用PCR／SSP方法对湖北省汉族病例组114例、对照组213例进行HLA-DRB基凶多态性分析，同时采用RT-heminested PCR方法对汉坦病毒（HV）进行病毒分型。结果HLA—DRB1^＊0401—0411、^＊1001、^＊1101-1105基因频率在HFRS患者组明显升高，分别为3．1％、2．2％、15．7％，与对照组比较，RR=13．87、9．72、2．00，χ^2=10．006、6．324、6．472，P〈0．05；DRB1^＊1501-1502、DRB4、DRB5基因频率在对照组分别为11．0％、19．0％、16．9％，与HFRS患者组比较，RR=0．45、0．58、0．23，χ^2=6．138、4．583、21．076，P〈0．05，而其他HLA-DRB基因频率差异无统计学意义。湖北地区为HV混合感染疫区且两型病毒多集中于江汉平原地区，汉滩型（THNV）略多于汉城型（SEOV），湖北地区HFRS患者中具有HLA—DRB1^＊1101—1105等位基因的有81．8％（27／33）为THNV感染，而SEOV感染只有18．2％，差异有统计学意义（P〈0．05）。结论湖北省汉族人中，HFRS与DRB1^＊0401—0411、^＊1001、^＊1101-1105呈正相关；HFRS与DRB1^＊1501-1502、DRB4、DRB5呈负相关。THNV的HV变异株在湖北地区具有一定的地理聚簇性。

Objective To understand the association of human leukocyte antigen （HLA）-DRB polymorphism and patients diagnosed as hemorrhagic fever with renal syndrome （HFRS）. Methods HLA-DR allele polymorphism was detected by PCR-sequence specific primers （PCR-SSP）. Hantavirus （HV） typed as Hantaan virus （HTNV） and Seoul virus （SEOV） in patients were detected by RT-heminested PCR. Results The gene frequency of DRB1^＊0401-0411, ^＊1001 and ^＊1101-1105 in HFRS case group were 3.1%, 2.2% and 15.7% respectively. Compared with control group, it was significant higher in HFRS case group （RR = 13.87, 9.72 and 2.00 respectively with Chi-square value as 10.006,6.324 and 6.472 respectively, P〈 0.05 ）. When compared with HFRS case group, the gene frequency of DRB1^＊1501-1502, DRB4 and DRB5 in control group were 11.0%, 19.0% and 16.9% respectively, markedly lower than in patients （RR=0.45, 0.58 and 0.23 respectively. Chi-square values were 6.138, 4.583 and 21.076 respectively, P〈0.05）. There was no significant difference in other HLA-DR gene frequencies. Mixed infection was found in Hubei, with HTNV slightly more than SEOV. Distinct hantaviruses could coexist in either different or the same geographic or ecological zores in Hubei province. Patients with HLA-DRB 1 ^＊ 1101-1105 alleles were 81.8% （27/33 ） infected by HTNV and only 18.2% infected by SEOV, which had significant difference （P〈0.05）. Conclusion DRB1^＊0401-0411, ^＊1001 and ^＊1101-1105 were possibly associated with increased susceptibility to HV infection. On the other hand there was an inverse correlation among HFRS, DRB1^＊1501-1502, DRB4 and DRB5.