The autophagy gene ATG16L1 (T300A) variant is associated with the risk and progression of HBV infection

Sharma, Alisha; Kaur, Sargeet; Duseja, Ajay; Changotra, Harish

doi:10.1016/j.meegid.2020.104404

Cited by 13 publications

(18 citation statements)

References 43 publications

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“…During the later stages of infection (CHB and cirrhosis), the polymorphism rs4958846 T/C plays a protective role in the disease pathogenesis. These results are consistent with our previous study on the role of the ATG16L1 gene (T300A) variant during various stages of HBV infection 27. In conclusion, although we could not find a significant difference in the levels of AST and ALT within the different genotypes of any of these SNPs, rs4958842 (À1,208 G/A) and rs4958846 (À947 T/C) were associated with the protection from HBV infection, whereas rs4958843 (À1,161 T/C) was associated with the infection risk in the CHB patients.…”

supporting

confidence: 94%

“…There was no substantial difference in age ( t = −0.448, p = 0.6546) and gender (χ 2 = 1.01, p = 0.31) between the cases and controls. Data from all the individuals enrolled in the study has been published previously 27 …”

Section: Resultsmentioning

confidence: 99%

“…37 We have recently shown that ATG16L1 T300A variant is associated with HBV infection risk and its progression. 27 In a genetic association study conducted in Han Chinese patients, variants in the intergenic region between PR domain zinc finger protein 1 and ATG5 were shown to be linked with HCC risk in individuals with CHB infection. 38 In one of our earlier studies, we in silico predicted the deleterious effect of various coding and non-coding variants of the ATG5 gene and further found a strong association of these genetic variants with HBV infection susceptibility (HC and AV, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…Informed consent was taken from the study subjects (infected and healthy individuals). Demographic details and study characteristics of all the participants have already been published elsewhere 27 . To attain the 80% power of the study required, the sample size was 385 subjects (http://www.raosoft.com/samplesize.html).…”

Section: Methodsmentioning

confidence: 99%

“…22 IRGM gene variants have been found to be associated with bacterial infection because they influence the autophagy-mediated antimicrobial defence. Several polymorphisms of autophagy genes have been reported to play role in the susceptibility of HBV infection, [23][24][25][26][27] but there is no study to date that has documented the involvement of IRGM polymorphisms in HBV infection. In the present study, we investigated the role of three polymorphisms (rs4958842, rs4958843, and rs4958846) present in the promoter region of IRGM in HBV infection susceptibility.…”

Section: Introductionmentioning

confidence: 99%

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Association of IRGM gene promoter polymorphisms with hepatitis B virus infection

Sharma

Duseja²,

Parkash

et al. 2022

The Journal of Gene Medicine

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Background In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. Methods We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Results Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co‐dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48–0.78; p = 0.0003), co‐dominant (OR = 0.52; 95% CI = 0.38–0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38–0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35–0.65, p = 0.0004), co‐dominant (OR = 0.38; 95% CI = 0.26–0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26–0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co‐dominant (OR = 1.52; 95% CI = 1.07–2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00–2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59–0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53–0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24–0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24–0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33–0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51–0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55–2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these p values mentioned here were obtained after performing Bonferroni correction. Conclusions In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population.

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supporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of IRGM gene promoter polymorphisms with hepatitis B virus infection

Sharma

Duseja²,

Parkash

et al. 2022

The Journal of Gene Medicine

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ATG5: A central autophagy regulator implicated in various human diseases

Changotra

Kaur

Yadav

et al. 2022

Cell Biochemistry & Function

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Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy‐independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy‐dependent and autophagy‐independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target.

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Autophagy‐related genes polymorphism in hepatitis B virus‐associated hepatocellular carcinoma: A systematic review

Yousefi,

Tabibzadeh,

Jawaziri

et al. 2024

Immunity Inflam & Disease

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BackgroundChronic hepatitis B (CHB) virus is the most common risk factor for developing liver malignancy. Autophagy is an essential element in human cell maintenance. Several studies have demonstrated that autophagy plays a vital role in liver cancer at different stages. In this systematic review, we intend to investigate the role of polymorphism and mutations of autophagy‐related genes (ATGs) in the pathogenesis and carcinogenesis of the hepatitis B virus (HBV).Materials and MethodsThe search was conducted in online databases (Web of Science, PubMed, and Scopus) using Viruses, Infections, Polymorphism, Autophagy, and ATG. The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses criteria.ResultsThe primary search results led to 422 studies. By screening and eligibility evaluation, only four studies were relevant. The most important polymorphisms in hepatocellular carcinoma were rs2241880 in ATG16L1, rs77859116, rs510432, and rs548234 in ATG5. Furthermore, some polymorphisms are associated with an increased risk of HBV infection including, rs2241880 in ATG16L1 and rs6568431 in ATG5.ConclusionThe current study highlights the importance of rs2241880 in ATG16L1 and rs77859116, rs510432, and rs548234 in ATG5 for HBV‐induced HCC. Additionally, some mutations in ATG16L1 and ATG5 were important in risk of HBV infection. The study highlights the gap of knowledge in the field of ATG polymorphisms in HBV infection and HBV‐induced HCC.

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The autophagy gene ATG16L1 (T300A) variant is associated with the risk and progression of HBV infection

Cited by 13 publications

References 43 publications

Association of IRGM gene promoter polymorphisms with hepatitis B virus infection

Association of IRGM gene promoter polymorphisms with hepatitis B virus infection

ATG5: A central autophagy regulator implicated in various human diseases

Autophagy‐related genes polymorphism in hepatitis B virus‐associated hepatocellular carcinoma: A systematic review

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