IFNL4 rs12979860 polymorphism influences HBV DNA viral loads but not the outcome of HBV infection in Moroccan patients

Chihab, Hajar; Badre, Wafaa; Tahiri, Mohamed; Jadid, Fatima-Zahra; Zaidane, Imane; Elfihry, Raouia; Marchio, Agnès; Pineau, Pascal; Ezzikouri, Sayeh

doi:10.1016/j.micinf.2021.104802

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…This is a pseudogene that, in some humans, encodes the interferon lambda 4 (IFNL4) proteins which is involved in immune response to viral infections. In prior reports, rs12979860 CC genotype was associated with lower hepatitis B virus plasma titers in Chinese and Moroccan patients treated with interferon-based therapy [33,34]. In other studies, IFNL4 rs12979860 CC genotype was independently associated with spontaneous HIV control in Caucasian Spanish individuals [35], but not in African Americans [36,37].…”

Section: Discussionmentioning

confidence: 87%

Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV

Cindi

Kawuma

Maartens

et al. 2023

Pharmacogenetics and Genomics

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Background Tenofovir is a component of preferred combination antiretroviral therapy (ART) regimens in Africa. Few pharmacogenetic studies have been conducted on tenofovir exposure in Africa, where genetic diversity is greatest. Objective We characterized the pharmacogenetics of plasma tenofovir clearance in Southern Africans receiving tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Methods Adults randomized to TAF or TDF in dolutegravir-containing arms of the ADVANCE trial (NCT03122262) were studied. Linear regression models stratified by study arm examined associations with unexplained variability in tenofovir clearance. We investigated genetic associations with polymorphisms selected a priori followed by genome-wide associations. Results A total of 268 participants (138 and 130 in the TAF and TDF arm, respectively) were evaluable for associations. Among polymorphisms previously associated with any drug-related phenotype, IFNL4 rs12979860 was associated with more rapid tenofovir clearance in both arms (TAF: P = 0.003; TDF: P = 0.003). Genome-wide, the lowest P values for tenofovir clearance in TAF and TDF arms were LINC01684 rs9305223 (P = 3.0 × 10−8) and intergenic rs142693425 (P = 1.4 × 10−8), respectively. Conclusion Among Southern Africans randomized to TAF or TDF in ADVANCE, unexplained variability in tenofovir clearance was associated with a polymorphism in IFNL4, an immune-response gene. It is unclear how this gene would affect tenofovir disposition.

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Section: Discussionmentioning

confidence: 87%

Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV

Cindi

Kawuma

Maartens

et al. 2023

Pharmacogenetics and Genomics

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“…The ∆G allele of (merged into ) was the risk factor for anti-HBs positive HBV patients, and the genotype ∆G/∆G decreased the responsiveness of HBV vaccination ( Grzegorzewska et al, 2020 ). Furthermore, the genotype of rs12979860 could modulate the HBV cccDNA levels located at the IFNL3 and IFNL4 genes ( Chihab et al, 2021 ). In our previous study, the LYM level was much higher in HBV patients with genotype CC of rs12979860 than in patients with genotype AA ( Song et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…The viral clearance of HCV patients treated with pegylated-IFN-α/ribavirin could be influenced by the genetic polymorphisms of the IFNL4 gene ( O’Brien et al, 2015 ). Similarly, the genetic polymorphisms in the IFNL4 gene were also associated with the viral load of HBV patients and protect individuals from HBV infection ( Chihab et al, 2021 ; Grzegorzewska et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China

Zheng

Shen

Xia

et al. 2022

PeerJ

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Hepatitis B virus (HBV) infection causes Hepatitis B, which is one of the most common causes of hepatocellular carcinoma (HCC). The single nucleotide polymorphisms (SNPs) of the host immune genes could impact HBV infection, viral clearance, and treatment effect. However, the contradictory roles of several studies suggest further analysis of various populations. The whole blood and biochemical indexes of 448 HBV patients and matched controls were collected from the Yunnan population to investigate the genetic roles of IFNL4 and the downstream genes (MxA and MxB). The genotypes, alleles, and haplotypes frequencies of the seven SNPs (rs11322783, rs117648444, rs2071430, rs17000900, rs9982944, rs408825, and rs2838029) from the HBV patients and controls were analyzed. However, no association was identified between the SNPs and HBV infection. Then, biochemical index levels were evaluated among the HBV patients with different genotypes of the seven SNPs. The results indicated that the liver function index levels (including alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), and albumin (ALB)) were influenced by the genotypes of the SNPs in HBV patients. Moreover, when the HBV patients were divided into HBsAg-positive and -negative groups, the association between the SNP genotypes and the biochemical indexes still existed. In addition, although the genetic polymorphisms in the IFNL4, MxA, and MxB genes were not significantly associated with HBV infection in the Yunnan population, these genes could indirectly influence disease progression by associating with the biochemical index levels of Yunnan HBV patients.

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Association Between IFN-λ4 rs12979860 And rs11322783 Polymorphisms with Spontaneous Clearance In Chronic Hepatitis B

Özkan,

Dalkılıç,

Kadıoğlu Dalkılıç

et al. 2024

Osmangazi̇ Journal of Medicine

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Many studies have been published on the association between IFN-λ3 and IFN-λ4 polymorphisms and treatment related or spontaneous clearance of chronic hepatitis C. To date there is little known about the impact of IFN-λ4 polymorphisms on the natural history of chronic hepatitis B(CHB). This study aimed to investigate the role of IFN-λ4 polymorphisms on the course of CHB and to influence the presence of spontaneous clearance (SC) in CHB patients. One hundred and twenty-two patients who had CHB, and 81 subjects who had spontaneous resolution of HBV were analyzed regarding IFN-λ4 rs12979860 and rs11322783 single‑nucleotide polymorphisms. We couldn’t found any significant difference between CHB groups and SC groups in terms of IFN-λ4 rs12979860 polymorphisms and, the CC, C/T and TT genotypes represented 49%, 45% and 5% of CHB patients and, %46, 43% and 11% of SC group respectively (p=0.65). On the other hand, in IFN-λ4 rs11322783 polymorphisms analysis, recessive G/G allele was more common in SC group compared to CHB group (5% vs 16%, p=0.04; OR: 3,55). Moreover, non-G/G genotypes had significantly higher in CHB patients compared to SC group (95% vs 84%, p=0.013; OR:3.55). Our results suggest that IFN-λ4 rs11322783 polymorphism may be a predictor of spontaneous clearance in HBV infected patients. The role of IFN-λ4 polymorphisms needs to be investigated in the natural history of HBV.

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IFNL4 rs12979860 polymorphism influences HBV DNA viral loads but not the outcome of HBV infection in Moroccan patients

Cited by 4 publications

References 43 publications

Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV

Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV

Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China

Association Between IFN-λ4 rs12979860 And rs11322783 Polymorphisms with Spontaneous Clearance In Chronic Hepatitis B

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