The Genetic Polymorphisms of HLA Are Strongly Correlated with the Disease Severity after Hantaan Virus Infection in the Chinese Han Population

摘要

The polymorphism of human leukocyte antigen (HLA), which is a genetic factor that influences the progression of hemorrhagic fever with renal syndrome (HFRS) after Hantaan virus (HTNV) infection, was incompletely understood. In this case-control study, 76 HFRS patients and 370 healthy controls of the Chinese Han population were typed for the HLA-A, -B, and -DRB1 loci. The general variation at the HLA-DRB1 locus was associated with the onset of HFRS (P < 0.05). The increasing frequencies of HLA-DRB1∗09 and HLA-B∗46-DRB1∗09 in HFRS patients were observed as reproducing a previous study. Moreover, the HLA-B∗51-DRB1∗09 was susceptible to HFRS (P = 0.037; OR = 3.62; 95% CI: 1.00–13.18). The increasing frequencies of HLA-B∗46, HLA-B∗46-DRB1∗09, and HLA-B∗51-DRB1∗09 were observed almost in severe/critical HFRS patients. The mean level of maximum serum creatinine was higher in HLA-B∗46-DRB1∗09 (P = 0.011), HLA-B∗51-DRB1∗09 (P = 0.041), or HLA-B∗46 (P = 0.011) positive patients than that in the negative patients. These findings suggest that the allele HLA-B∗46 and haplotypes HLA-B∗46-DRB1∗09 and HLA-B∗51-DRB1∗09 in patients could contribute to a more severe degree of HFRS and more serious kidney injury, which improve our understanding of the HLA polymorphism for a different outcome of HTNV infection.