Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome

PLoS Negl Trop Dis. 2016 Oct 19;10(10):e0005076. doi: 10.1371/journal.pntd.0005076. eCollection 2016 Oct.

Abstract

Objective: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.

Methods: A total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf's method.

Results: A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).

Conclusion: The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bunyaviridae Infections / blood
  • Bunyaviridae Infections / genetics*
  • Bunyaviridae Infections / virology
  • Female
  • Gene Frequency*
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA-A Antigens / genetics*
  • HLA-B Antigens / genetics*
  • HLA-DRB1 Chains / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Phlebovirus* / isolation & purification
  • Polymerase Chain Reaction
  • Polymorphism, Genetic

Substances

  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DRB1 Chains

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81102171), (http://www.nsfc.gov.cn) to SJD, Shandong Medical Science and Technology Development Program (Grant No. 2011HZ055), (http://www.sdws.gov.cn) to SJD, Shandong Province Science and Technology Development Plan (Grant No. 2012GHZ30031), (http://www.sdstc.gov.cn) to XMZ, and the Shandong Natural Science Foundation of China (Grant No.ZR2014HP030),(http://www.sdstc.gov.cn/eggs/1000007923.htm) to XlJ.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.