A non-synonymous variant rs12614 of complement factor B associated with risk of chronic hepatitis B in a Korean population

Abstract Background: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.Methods: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1,716 study subjects comprised of 955 CHB patients and 761 population controls. Results: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91×10-10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS. Conclusions: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.

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A Non-Synonymous Variant rs12614 of Complement Factor B Associated with Risk of Chronic Hepatitis B in a Korean Population

10.21203/rs.3.rs-48397/v2 ◽

2020 ◽

Author(s):

Jung Yeon Seo ◽

Joong Gon Shin ◽

Byeong Ju Youn ◽

Suhg Namgoong ◽

Hyun Sub Cheong ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Association Study ◽

Genetic Effect ◽

Korean Population ◽

Complement Factor ◽

Single Nucleotide ◽

Factor B ◽

Synonymous Variant ◽

Population Controls

Abstract Background: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.Methods: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1,716 study subjects comprised of 955 CHB patients and 761 population controls. Results: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91×10-10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS. Conclusions: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.

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A Non-Synonymous Variant of Complement Factor B Associated with Risk of Chronic Hepatitis B in a Korean Population

10.21203/rs.3.rs-48397/v1 ◽

2020 ◽

Author(s):

Jung Yeon Seo ◽

Joong Gon Shin ◽

Byeong Ju Youn ◽

Suhg Namgoong ◽

Hyun Sub Cheong ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Association Study ◽

Chronic Hepatitis B ◽

Genetic Effect ◽

Korean Population ◽

Complement Factor ◽

Factor B ◽

Synonymous Variant ◽

Population Controls

Abstract Background: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.Methods: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1,716 study subjects comprised of 955 CHB patients and 761 population controls. Results: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91×10-10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS. Conclusions: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.

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IL17A gene polymorphisms: relationship to predisposition for chronic viral hepatitis and progression to liver cirrhosis in kazakh population

Voprosy Virusologii ◽

10.18821/0507-4088-2016-61-5-212-219 ◽

2016 ◽

Vol 61 (5) ◽

pp. 212-219

Author(s):

M. R. Massabayeva ◽

N. E. Aukenov ◽

Zh. B. Mussazhanova ◽

V. A. Saenko ◽

T. I. Rogounovitch ◽

...

Keyword(s):

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Single Nucleotide Polymorphisms ◽

Viral Hepatitis ◽

Association Study ◽

Chronic Viral Hepatitis ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Kazakh Population

Introduction. This work is the first genetic association study of a potential relationship of single nucleotide polymorphisms rs8193036 and rs2275913 located in the IL17A promoter on chromosome 6p12 to chronic viral hepatitis and its progression in Kazakh population. Purpose. Evaluation of the effect of IL17A polymorphism on predisposition for chronic hepatitis B and C and its progression to liver cirrhosis. Material and methods. A total of 862 individuals were enrolled in the retrospective case-control association study. Among the participants, 100 patients had chronic hepatitis B and/or C and liver cirrhosis, and 341 patients had chronic viral hepatitis only. Four hundred twenty-one (421) healthy HBV- and HCV-negative donors without liver diseases were recruited as population control. single nucleotide polymorphisms rs8193036[T/C] and rs2275913[G/A] were genotyped by TaqMan assays using genomic DNA extracted from peripheral blood cells. Results. Minor allele frequencies of rs8193036[C] and rs2275913[A] in the groups of patients were very similar to those observed in the control population, 0.4 and 0.3, respectively. Multivariate logistic regression analysis revealed odds ratios close to 1.0 and confidence intervals overlapping with the value of 1.0 and statistical significance p > 0.4 for any groups under comparison in the multiplicative model of inheritance. Conclusion. No significant association between two single nucleotide polymorphisms, rs8193036 and rs2275913 in the IL17A promoter, and susceptibility to chronic viral hepatitis C and/or B and disease progression to liver cirrhosis in Kazakh population were found.

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A missense variant in complement factor B (CFB ) is a potential predictor of 24-week off-treatment response to PegIFNα therapy in Chinese HBeAg-positive chronic hepatitis B patients

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.15624 ◽

2020 ◽

Vol 51 (4) ◽

pp. 469-478 ◽

Cited By ~ 1

Author(s):

Haitao Chen ◽

Jian Sun ◽

Bin Zhou ◽

Jinxin Peng ◽

Qing Xie ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Treatment Response ◽

Chronic Hepatitis B ◽

Missense Variant ◽

Complement Factor ◽

Factor B ◽

Potential Predictor ◽

Complement Factor B ◽

Positive Chronic Hepatitis

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Associations between the single nucleotide polymorphisms of APOBEC3A, APOBEC3B and APOBEC3H, and chronic hepatitis B progression and hepatocellular carcinoma in a Chinese population

Molecular Medicine Reports ◽

10.3892/mmr.2019.10455 ◽

2019 ◽

Author(s):

Xiuting He ◽

Hongqin Xu ◽

Xiaomei Wang ◽

Jing Wu ◽

Junqi Niu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Single Nucleotide Polymorphisms ◽

Chronic Hepatitis B ◽

Chinese Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz084 ◽

2019 ◽

Vol 69 (11) ◽

pp. 1969-1979

Author(s):

Willem P Brouwer ◽

Henry L Y Chan ◽

Pietro Lampertico ◽

Jinlin Hou ◽

Pisit Tangkijvanich ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Association Study ◽

Chronic Hepatitis B ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Pegylated Interferon ◽

Hbv Dna ◽

Genome Wide Association ◽

Genome Wide

AbstractBackground(Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand.MethodsIn this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients.ResultsOf 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele.ConclusionsAlthough no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies.Clinical Trials RegistationNCT01401400.

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