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

Genetics and Molecular Biology

Janaina Mota De Vasconcelos²  Lizomar De Jesus Maués Pereira Móia¹  Ivanete Do Socorro Abraçado Amaral¹  Esther Castello Branco Mello Miranda¹  Louise Yukari Cicalisetakeshita²  Layanna Freitas De Oliveira²  Lilian De Araújo Melo Mendes²  Danuta Sastre²  Bruna Pedroso Tamegão-lopes²  Larysse Santa Rosa De Aquino Pedroza²  Sidney Emanuel Batista Dos Santos²  Manoel Do Carmo Pereira Soares¹  Marialva Tereza Ferreira De Araújo¹  Camila Lucas Bandeira¹  Adriana Maria Paixão De Sousa Da Silva¹  Zilene Lameira De Medeiros¹  Leonardo Sena²  Samia Demachki¹  Eduardo José Melo Dos Santos² 

[1] ,Universidade Federal do Pará Instituto de Ciências Biológicas Belém PA ,Brazil

关键词: HCV;    KIR;    HLA-C;    hepatitis C;    KIR2DL2;   

DOI  :  10.1590/S1415-47572013000100004

来源: SciELO

【 摘 要 】

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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