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

Abstract EN

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.