RESUMO
The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon. In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT). A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection. These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.
RESUMO
Over 325 million people worldwide are living with hepatitis B and C viral infections and are at greater risk of developing hepatocellular carcinoma. The interactions between killer cell immunoglobulin-like receptors (KIRs) and their cognate ligands, human leukocyte antigens, modulate both infection processes and disease progression. We report here (1) genotype and haplotype variations in KIR genes in Cameroon and (2) their impact on susceptibility to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. In 98 unrelated individuals (33 HCV+, 31 HBV+, and 34 uninfected healthy controls), we determined the presence of 15 KIR genes by polymerase chain reaction-sequence-specific primer techniques. One pseudogene and all 14 KIR genes were present. We identified 36 KIR genotypes, 5 of which have not been previously reported in public databases. Two inhibitory (KIR2DL1 and KIR2DL3) and three activating (KIR2DS4, KIR2DS2, and KIR2DS3) genes were present in all HCV-infected individuals. Similarly, KIR3DL1, KIR2DL1, and KIR2DS4 were present at 100% in the HBV+ group. Compared with uninfected healthy controls, the frequencies of KIR2DL2 and KIR3DS1 were significantly lower in the HBV+ group (p = 0.003 and p < 0.001, respectively). Conversely, KIR3DS1 was significantly overrepresented in the HCV+ group compared with controls (97.0% vs. 64.7%, respectively, p < 0.001). These results may imply that KIR3DS1 carriers were less likely to be HBV infected, but may be predisposed to HCV infection compared with uninfected controls, indicating their important role in transmission of these viruses. However, phenotypic, functional, and genomic studies to elucidate the role of these KIR genotypes and haplotypes in infection with HBV and HCV are important.