Genetics and Molecular Biology (Jan 2013)

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

  • 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

Journal volume & issue
Vol. 36, no. 1
pp. 022 – 027

Abstract

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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.

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