Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

soroprevalence for hepatitis c virus is reported as 2.12% in northern brazil, with about 50% of the patients exhibiting a sustained virological response (svr). aiming to associate polymorphisms in killer cell immunoglobulin-like receptors (kir) with chronic hepatitis c and therapy responses we investigated 125 chronic patients and 345 controls. additionally, 48 ancestry markers were genotyped to control for population stratification. the frequency of the kir2dl2 and kir2dl2+hla-casp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, or = 3.4; p = 0.001, or = 3.45). in fact, kir2dl3 is a weaker inhibitor of nk activity than kir2dl2, which could explain the association of kir2dl2 with chronic infection. moreover, kir2ds2 and kir2ds2+hla-casp80 (p < 0.0001, or = 2.51; p = 0.0084, or = 2.62) and kir2ds3 (p < 0.0001; or = 2.57) were associated with chronic infection, independently from kir2dl2. no differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. the allelic profile kir2dl2/kir2ds2/kir2ds3 was associated with the chronic hepatitis c (p < 0.0001; or = 3). furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous aa profile, which is likely secondary to the association with non-aa and/or activating genes. in addition, the kir2ds5 allele was associated with svr (p = 0.0261; or = 0.184).the ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies.