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Association of HLA-DP/DQ, STAT4 and IL-28B variants with HBV viral clearance in Tibetans and Uygurs in China.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2015 Mar; Vol. 35 (3), pp. 886-96. Date of Electronic Publication: 2014 Aug 05. - Publication Year :
- 2015
-
Abstract
- Background & Aims: Several genome-wide association studies have revealed that HLA-DP/DQ, STAT4 and IL-28B associated with liver diseases. But because of population heterogeneity, different races would have different causative polymorphisms. Therefore, in this study, we included Chinese Tibetans and Uygurs to examine the roles of these genes on HBV natural clearance.<br />Methods: A total of 1341 subjects including 908 Tibetans and 433 Uygurs were recruited. Seven single nucleotide polymorphisms (SNP) were genotyped.<br />Results: HLA-DP/DQ polymorphisms associated with HBV natural clearance in both ethnicities (Tibetans, rs3077, OR = 0.61, 95% CI = 0.46-0.82; rs9277535, OR = 0.56, 95% CI = 0.41-0.75; rs7453920, OR = 0.64, 95%CI = 0.47-0.85; Uygurs, rs3077, OR = 0.48, 95% CI = 0.24-0.96; rs9277535, OR = 0.43, 95% CI = 0.20-0.91; rs7453920, OR = 0.62, 95% CI = 0.39-0.99), whereas no significant association was observed between IL-28B with HBV natural clearance in neither ethnicities (P > 0.05). STAT4 rs7574865 seemed to be Tibetan specific in HBV natural clearance (OR = 0.76, 95% CI = 0.58-0.99). Moreover, in Tibetan patients, HLA-DQ rs7453920 GG had a higher frequency in HBeAg positive patients (P = 0.032) and STAT4 rs7574865 GG genotype appeared more frequently in Genotype C virus infected patients (P = 0.005). In addition, Uygurs have higher frequencies of HLA-DP/DQ protective alleles (72.5% for rs3077, 76.6% for rs9277535 and 26.8% for rs7453920) than Tibetans (51.7% for rs3077, 52.5% for rs9277535 and 18.5% for rs7453920)(all P < 0.05), and a lower prevalence of HBV infection as previously reported.<br />Conclusions: HLA-DP/DQ but not IL-28B polymorphisms correlate with HBV natural clearance, irrespective of race, and HLA-DP/DQ would be causative genes attributing to varying prevalence in different regions. STAT4 rs7574865 seemed to be population specific in Tibetans and it might synergistically interact with virus contributing to disease progression.<br /> (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Case-Control Studies
China
Female
Gene Frequency
Haplotypes
Hepatitis B immunology
Hepatitis B virology
Hepatitis B e Antigens blood
Hepatitis B virus genetics
Humans
Interferons
Male
Middle Aged
Polymorphism, Genetic
Tibet ethnology
Viral Load
Young Adult
HLA-DP Antigens genetics
HLA-DQ Antigens genetics
Hepatitis B genetics
Interleukins genetics
STAT4 Transcription Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 25041342
- Full Text :
- https://doi.org/10.1111/liv.12643