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

摘要

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 = 1.05 E ? 05; OR?=?23.99) and B?35:01:01-C?07:02.01 ( p = 4.15 E ? 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.