Fine-mapping butyrophilin family genes revealed several polymorphisms influencing viral genotype selection in hepatitis C infection.
Host-viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
J
J
Ampuero
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
J A
JA
del Campo
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
L
L
Rojas
Immunology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
R J
RJ
García-Lozano
Hepatology Unit, Hospital Vall d'Hebron and CIBERehd, Barcelona, Spain.
M
M
Buti
Digestive Department, Hospital del Mar, Barcelona, Spain.
R
R
Solá
Liver Unit and IDIBAPS, Hospital Clinic and CIBERehd, Barcelona, Spain.
X
X
Forns
Digestive Department, Hospital de la Princesa, Madrid, Spain.
R
R
Moreno-Otero
Gastroenterology Department, Hospital Virgen de la Victoria and CIBERehd, Málaga, Spain.
R
R
Andrade
Digestive Department, Hospital General de Valencia, Valencia, Spain.
M
M
Diago
Digestive Department, Hospital Universitario San Cecilio and CIBERehd, Granada, Spain.
J
J
Salmerón
Gastroenterology Department, Hospital Central de Asturias, Oviedo, Spain.
L
L
Rodrigo
Gastroenterology Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
J A
JA
Pons
Gastroenterology Department, Hospital Costa del Sol, Marbella, Spain.
J M
JM
Navarro
Liver Unit, Hospital Puerta de Hierro, Madrid, Spain.
J L
JL
Calleja
Hepatology Unit, Hospital Carlos III & CIBERehd, Madrid, Spain.
J
J
García-Samaniego
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
M
M
García-Valdecasas
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
Á
Á
Rojas
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
R
R
Millán
Immunology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
M F
MF
González-Escribano
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Sevilla, Spain.
M
M
Romero-Gómez
D000071797:Butyrophilins; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
D000071797:Butyrophilins; D008562:Membrane Glycoproteins