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HLA and KIR polymorphism among patients with chronic hepatitis C

The HLA and KIR complexes, as two major factors of immune system, influence the course of numerous infectious diseases. The of the study was to investigate the association of these genetic systems' polymorphism with hepatitis C virus (HCV) infection. HLA class I and II genes (HLA-A, -B, - C, -DRB1 and -DQB1) as well as KIR genes (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, and KIR3DS1)and pseudogenes (KIR2DP1, KIR3DP1) were analyzed for 59 patients listed for liver transplantation with a ETRL code D04 (Cirrhosis - Virus C related cirrhosis)and 214 healthy control individuals using high resolution molecular HLA typing methods. Comparison of allele frequencies revealed a significantly increased frequency among patients for HLA-DRB1*15:01 and *15:02 alleles(P=0.048, P=0.042, respectively), HLA- DRB1*15 specificity (P=0.007) ; and HLA- DQB1*06:01 allele(P=0.042). Two-locus haplotype analysis demonstrated an increased occurrence of following haplotypes among patients: HLA- A*01:01~B*07:02 (P=0.033), HLA-A*03:01~B*35:01 (P=0.021), HLA-B*35:01~C*04:01(P=0.031), HLA- B*37:01~C*06:02 (P=0.033), HLA-B*51:01~C*12:03 (P=0.010), HLA-B*35:01~DRB1*16:01(P=0.010), HLA- B*44:02~DRB1*13:02 (P=0.010), HLA- B*51:01~DRB1*08:01 (P=0.010), HLA- B*52:01~DRB1*15:02 (P=0.010), HLA- B*18:01~DRB1*15:01 (P=0.003), HLA- DRB1*15:02~DQB1*06:01(P=0.003), HLA- DRB1*15:01~DQB1*05:02 (P=0.009). Among KIR genes, only the increase of the KIR2DS4 deletion variant frequency among patients was significant (P=0.0331). None of the observed differences retained statistical significance after correction of P value for multiple comparisons. In conclusion, although numerous observed differences in distribution of HLA and KIR polymorphisms between HCV patients and controls suggest a possible role of these systems in HCV infection. Future studies should include a larger number of patients in order to reliably determine their importance for this viral infection.

HLA, KIR, chronic hepatitis C

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