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The interferon receptor‐1 promoter polymorphisms affect the outcome of Caucasians with HB eAg‐negative chronic HBV infection
Author(s) -
Karamitros Timokratis,
Papatheodoridis George,
Dimopoulou Eleni,
Papageorgiou MariaVasiliki,
Paraskevis Dimitrios,
Magiorkinis Gkikas,
Sypsa Vana,
Hatzakis Angelos
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12859
Subject(s) - genotype , single nucleotide polymorphism , hepatitis b virus , variable number tandem repeat , immunology , allele , medicine , hbeag , biology , virology , virus , gene , genetics , hbsag
Background & Aims The outcome of HB eAg‐negative chronic hepatitis B virus ( HBV ) patients who may remain in the inactive carrier state ( IC ) or progress to HB eAg‐negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within not only the promoter but also the coding sequence of the interferon receptor 1 ( INFAR 1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HB eAg‐negative patients has not been evaluated. We examined the association of INFAR 1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HB eAg‐negative chronic HBV patients. Methods Using a combination of conventional and allele‐specific polymerase chain reactions, bidirectional sequencing and DNA ‐fragment analysis, we performed typing of three Single Nucleotide Polymorphisms ( SNP s ‐568G/C, ‐408C/T, ‐3C/T) and one Variable Number Tandem Repeat [ VNTR ‐77( GT )n] within the INFR 1 promoter sequence. Results The genetic polymorphisms examined were found to be associated with the phase of HB eAg‐negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes ‐408 CT _‐3 CT were more likely to be IC s ( OR = 2.42 vs. CC , P = 0.036). Also, given the partial linkage between SNP ‐568G/C and VNTR ‐77( GT )n, we found that linked genotypes ‐77( GT )n ≤ 8/≤8_‐568 GC and ‐77( GT )n ≤ 8/≤8_‐568 CC were detected more frequently among IC s ( OR = 11.69, P = 0.005 and OR = 7.56, P = 0.001 vs. ‐77( GT )n >8/>8_‐568 GG respectively). Conclusions These findings suggest that these genetic variations represent important factors associated with the clinical phase of HB eAg‐negative chronic HBV infection.