title: Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil.
abstract: 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-C(Asp80) 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-C(Asp80) (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.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Janaina Mota
authors.initials: JM
authors.lastname: de Vasconcelos
authors.forename: Lizomar
authors.initials: L
authors.lastname: de Jesus Maués Pereira Móia
authors.forename: Ivanete do Socorro Abraçado
authors.initials: Ido S
authors.lastname: Amaral
authors.forename: Esther Castello Branco Mello
authors.initials: EC
authors.lastname: Miranda
authors.forename: Louise Yukari
authors.initials: LY
authors.lastname: Cicalisetakeshita
authors.forename: Layanna Freitas
authors.initials: LF
authors.lastname: de Oliveira
authors.forename: Lilian
authors.initials: L
authors.lastname: de Araújo Melo Mendes
authors.forename: Danuta
authors.initials: D
authors.lastname: Sastre
authors.forename: Bruna Pedroso
authors.initials: BP
authors.lastname: Tamegão-Lopes
authors.forename: Larysse Santa Rosa
authors.initials: LS
authors.lastname: de Aquino Pedroza
authors.forename: Sidney Emanuel
authors.initials: SE
authors.lastname: Batista Dos Santos
authors.forename: Manoel do Carmo Pereira
authors.initials: Mdo C
authors.lastname: Soares
authors.forename: Marialva Tereza Ferreira
authors.initials: MT
authors.lastname: de Araújo
authors.forename: Camila Lucas
authors.initials: CL
authors.lastname: Bandeira
authors.forename: Adriana Maria Paixão
authors.initials: AM
authors.lastname: de Sousa da Silva
authors.forename: Zilene Lameira
authors.initials: ZL
authors.lastname: de Medeiros
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sena
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.forename: Eduardo José Melo
authors.initials: EJ
authors.lastname: Dos Santos
keywords: HCV; HLA-C; KIR; KIR2DL2; hepatitis C