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

• Main Authors: Janaina Mota de Vasconcelos, Lizomar de Jesus Maués Pereira Móia, Ivanete do Socorro Abraçado Amaral, Esther Castello Branco Mello Miranda, Louise Yukari CicaliseTakeshita, Layanna Freitas de Oliveira, Lilian de Araújo Melo Mendes, Danuta Sastre, Bruna Pedroso Tamegão-Lopes, Larysse Santa Rosa de Aquino Pedroza, Sidney Emanuel Batista dos Santos, Manoel do Carmo Pereira Soares, Marialva Tereza Ferreira de Araújo, Camila Lucas Bandeira, Adriana Maria Paixão de Sousa da Silva, Zilene Lameira de Medeiros, Leonardo Sena, Samia Demachki, Eduardo José Melo dos Santos
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Genética 2013-01-01
• Series: Genetics and Molecular Biology
• Subjects: HCV; KIR; HLA-C; hepatitis C; KIR2DL2
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572013000100004
• ISSN: 1415-4757; 1678-4685

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.