Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population

Rauff, Bisma; Amar, Ali; Chudhary, Shafiq Ahmad; Mahmood, Saqib; Tayyab, Ghias Un Nabi; Hanif, Rumeza

doi:10.1007/s00705-020-04901-2

Cited by 4 publications

(6 citation statements)

References 73 publications

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“…The findings of interest were that age greater than 40 years and male sex, progressive factors in chronic HBV infection, are also protective factors in primary infection, suggesting that males above the age of 40 have immune capacity that assists with natural clearance in primary HBV infection. Consistent with previous findings, adults and males are predisposed to resolve spontaneously, while males at earlier-onset puberty with primary HBV infection are shown to be associated with chronicity, immune tolerance, and greater HBV-DNA load [26].…”

Section: Discussionsupporting

confidence: 90%

Polymorphism of IFNL3 rs12979860 associated immunity establishment in primary HBV infection: a multicenter study

Yao,

Sun,

et al. 2024

Preprint

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The polymorphisms of IFNL3 associated with the outcomes of primary HBV infection remains controversial, the susceptibility has not been investigated across cohorts. So two cohorts, including 3874 participants, were enrolled to detect the association of IFNL3 genetic variants (rs12979860, rs12980275, and rs809917) with outcomes of primary HBV infection between groups of chronic HBV infection (CHB), Natural clearance (NC), Health control (HC), and a false-positive report probability (FPRP) test was applied to assess positive results, and function prediction of significant polymorphism was evaluated. Polymorphism of rs12979860 demonstrated a correlation to the outcomes of primary infection. In comparison between NC and CHB, the rs12979860-C significantly decreased the risk of CHB as compared to T allele in Hubei, Hainan and combined two cohorts, and in HC vs. NC comparison, the allele of rs12979860-C also refers immunity establishment against HBV in comparison to T allele in Hubei, Hainan, and combined two cohorts. In comparison between NC and CHB, the rs12979860-TT genotypes significantly increased the risk of CHB in Hubei, Hainan and combined two cohort. After adjusting the influence of age and sex, the results remain significant. FPRP test confirms the significance of rs12979860, moreover, rs12979860-C/T alteration brings the minimum free energy change in the centroid secondary structure. The polymorphism of rs12979860 in IFNL3 is associated with primary outcomes of HBV infection, and rs12979860-CC is associated with immunity establishment in primary HBV infection, serving as potential predictors against virus infection.

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Section: Discussionsupporting

confidence: 90%

Polymorphism of IFNL3 rs12979860 associated immunity establishment in primary HBV infection: a multicenter study

Yao,

Sun,

et al. 2024

Preprint

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“…The baseline data of the present sample set has been described elsewhere [19] and is summarized below. Briefly, among a total of 502 CHC patients, median age was 40 years and there were less men (47.9%) included in the sample set than women.…”

Section: Resultsmentioning

confidence: 99%

“…The details of ethical approvals and consent, patients and samples and their clinical and laboratory evaluations pertaining to this study have been described previously [19]. Briefly, in this cross-sectional comparative study, 502 Pakistani patients with CHC (treatment naive) presenting at a tertiary care hospital in Lahore, Pakistan, were recruited.…”

Section: Patients and Samplesmentioning

confidence: 99%

“…CHC patients were evaluated for hepatic fibrosis and cirrhosis based on imaging analysis i.e. transient elastography by Fibroscan ® (Echosens, Waltham, North America) with probes SN77561 and SN94171, where Ziol transient elastography cut-offs [20] were used to define Metavir fibrosis stages (F0-F3) and cirrhosis (F4) with maximal sensitivity and specificity as used previously [19,21]. Based on the Metavir fibrosis stages, the significant hepatic fibrosis was defined as ≥ F2, advanced hepatic fibrosis as ≥ F3 and hepatic cirrhosis as F4.…”

Section: Patients and Samplesmentioning

confidence: 99%

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PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study

et al. 2022

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Background The present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients. Methods In total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated. Results Genotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy–Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis (p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load (p = > 0.05). Conclusions PNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.

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“…SNPs in the INFL3-INFL4 region, rs12979860, rs4803217 and rs368234815 were determined as a powerful foreteller of HCV clearance [27][28][29]. Several reports showed the genetic and functional association of these variants with liver fibrosis in different ethnicities [30][31][32]. This association was found with other hepatic infection, like HBV [33,34], other hepatic illnesses, like non-alcoholic fatty liver (NAFLD) [33,35], and even other organs fibrosis [36,37].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in INFL3-INFL4 region are associated with fibrosis and cirrhosis in Egyptian patients with chronic hepatitis C

Thabit,

Bkeet,

Abdelhalem

et al. 2023

Journal of advanced Biomedical and Pharmaceutical Sciences

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Genetic variables have a notable and polygenic impact on the incidence and development of hepatic fibrosis and cirrhosis in individuals with chronic hepatitis C (CHC). Genetic polymorphisms in interferon-λ3-interferon-λ4 (INFL3-INFL4) region, rs12979860 and its highly linked disequilibrium polymorphisms (rs368234815 and rs4803217) are linked to liver inflammation and fibrosis progression in CHC individuals from different ethnic groups. For Egyptian patients, no data available about the degree of linkage disequilibrium between these variants and their effect on liver fibrosis. In this study, 99 healthy controls and 176 CHC patients were genotyped for 3 variants in (INFL3-INFL4) region rs12979860, rs4803217, and rs368234815. We found that these variants are highly linked disequilibrium in Egyptian CHC cohort. Moreover, we found that the major alleles of these 3 polymorphisms (rs12979860, rs4803217, and rs368234815) significantly increase the risk of liver fibrosis (P = 0.015, 0.026, and 0.007 respectively). Additionally, these variants were linked to stage of hepatic fibrosis. This report shows that the 3 linked disequilibrium variants in INFL3-INFL4 region may be valuable foretellers of liver fibrosis and cirrhosis in CHC Egyptian patients.

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Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population

Cited by 4 publications

References 73 publications

Polymorphism of IFNL3 rs12979860 associated immunity establishment in primary HBV infection: a multicenter study

Polymorphism of IFNL3 rs12979860 associated immunity establishment in primary HBV infection: a multicenter study

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study

Single nucleotide polymorphisms in INFL3-INFL4 region are associated with fibrosis and cirrhosis in Egyptian patients with chronic hepatitis C

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