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

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.