An Increased Frequency in HLA Class I Alleles and Haplotypes Suggests Genetic Susceptibility to Influenza A (H1N1) 2009 Pandemic: A Case-Control Study

J Immunol Res. 2018 Feb 25:2018:3174868. doi: 10.1155/2018/3174868. eCollection 2018.

Abstract

Background: The influenza A H1N1/09 pandemic infected a small number of exposed individuals, which suggests the involvement of genetic factors. There are scarce data available on classical HLA class I association with the influenza A H1N1/09 pandemic.

Methods: We analyzed the frequency of classical HLA class I alleles and haplotypes in A H1N1/09 influenza in a case-control study including 138 influenza patients (INF-P) and 225 asymptomatic healthy contacts (INF-C) simultaneously recruited. HLA class I typing was performed by high-resolution sequence-based typing method.

Results: Our analysis revealed higher frequency of C∗07:02:01, B∗39:06:02, C∗03:02:01, B∗44:03:01, B∗51:01:05, and B∗73:01 (p < 0.05; OR = 1.84-9.98) and of two haplotypes-A∗68:01:02-C∗07:02:01 (p = 1.05E - 05; OR = 23.99) and B∗35:01:01-C∗07:02.01 (p = 4.15E - 04, OR = 2.15)-in A H1N1/09 influenza subjects. A∗68:01:01 was exclusively present only in the INF-P group (5/138). A decrease in the frequency of C∗03:03:01, A∗11:01:01, B∗39:01:01, A∗24:02:01, C∗03:04:01, B∗51:01:01, and C∗07:01:01 (p < 0.05; OR = 0.12-0.52) and of haplotypes A∗02:01:01-B∗35:01:01-C∗04:01:01, A∗24:02:01-B∗35:01:01, B∗39:01:01-C∗07:02:01, and B∗40:02:01-C∗03:04:01 (p < 0.05; OR = 0.08-0.22) were observed in INF-P group.

Conclusion: Selective classical HLA class I allele and haplotype combinations predispose individuals towards susceptibility or protection against the influenza A H1N1/09 pandemic. This work has significant implications for accessing population transmission risk for A H1N1/09 or a similar strain breakout in the future.

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype*
  • HLA Antigens / genetics*
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Testing
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza, Human / epidemiology
  • Influenza, Human / genetics*
  • Influenza, Human / mortality
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Pandemics
  • Survival Analysis
  • Viral Load

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I