Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study

Jiménez‐Sousa, María A.; Gómez-Moreno, Ana Zaida; Pineda‐Tenor, Daniel; Sánchez-Ruano, Juan José; Artaza-Varasa, Tomas; Martín-Vicente, María; Fernández‐Rodríguez, Amanda; Martı́nez, Isidoro; Resino, Salvador

doi:10.3390/biom9040143

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…A preliminary retrospective study was performed in 208 patients from the Hospital Virgen de la Salud (Toledo, Spain). All patients suffered from chronic hepatitis C and were enrolled between 2008 and 2016, as previously described (see Supplementary Figure 1 ) ( 23 ).…”

Section: Methodsmentioning

confidence: 99%

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

Pineda‐Tenor¹,

Gómez-Moreno

Sánchez-Ruano

et al. 2020

Front. Med.

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Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models. Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83–0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19–0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68–0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06–0.74; p = 0.015). Conclusions: MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.

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Section: Methodsmentioning

confidence: 99%

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

Pineda‐Tenor¹,

Gómez-Moreno

Sánchez-Ruano

et al. 2020

Front. Med.

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“…However, the findings of a study conducted by Jiménez-Sousa et al (25) were inconsistent. In their retrospective cohort study (based on a repeated measures design) performed on 208 chronic HCVinfected patients, rs12075 was correlated with the liver fibrosis progression in HCV-infected patients.…”

Section: Discussionmentioning

confidence: 88%

Relationship between Duffy Antigen Receptor for Chemokines and Clinical Characteristics in Han People with Chronic Hepatitis C Infection in Dalian, China

Shao¹,

Zhou²,

Liu

2020

ircmj

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Background and Objectives: Most patients with untreated chronic hepatitis C virus (HCV) infection develop hepatic fibrosis. Hepatic disease progression is monitored with hematological markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin and platelet [PLT] count, AST/ALT ratio, AST/PLT ratio index [APRI], and fibrosis 4 score [FIB-4]) and FibroScan. The present study aimed to investigate the association between Duffy antigen/chemokines receptor (DARC) polymorphisms and clinical parameters in the Han people with chronic hepatitis C infection in Dalian, China. Materials and Methods: This cohort study was performed on 245 Han people with chronic HCV at Dalian infectious hospital during April-December 2015. The participants of the research were selected using the consecutive sampling method. The DARC genotyping was performed using the TaqMan probe method and transient elastography was measured by FibroScan. Results: Based on the findings, DARC polymorphisms correlated with ALT concentrations (FY*A/FY*A vs. FY*A/FY*B, P=0.025). However, the DARC polymorphism did not have an association with HCV RNA titers (FY*A/FY*A vs. FY*A/FY*B, P=0.241) or hepatic fibrosis (FY*A/FY*A vs. FY*A/FY*B, P=0.325). Moreover, correlation analyses showed that APRI (P<0.001, rho=0.603) and FIB-4 (P<0.001, rho=0.698) were useful predictors of hepatic fibrosis in chronic HCV infection. Besides, HCV RNA titers (P=0.327) and hepatic injury markers (P=0.814, 0.198, 0.767, and 0.171 for ALT, AST, ALB, and AST/ALT, respectively) were not useful for the estimation of the fibrosis stage in patients with chronic hepatitis C. Conclusion: The FY*A allele is a potentially valuable protective factor against hepatocyte damage in chronic HCV-infected patients.

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“…We found that patients carrying rs886277 C allele and CC genotype had an increased risk of liver fibrosis progression and cirrhosis development. The association found between TRPM5 rs886277 polymorphism and liver fibrosis and cirrhosis was independent of the effect of other SNPs, since logistic regression models were adjusted by the most relevant covariables, including five SNPs previously reported in this cohort ( MERTK rs4374383 [ 37 ], PNPLA3 rs738409 [ 38 ], IL7RA rs6897932 [ 35 ], MTHFR rs1801133 [ 39 ], and DARC rs12075 [ 30 ]). These five SNPs were related to liver fibrosis progression and development of cirrhosis [ 30 , 35 , 37 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 94%

“…We conducted a retrospective study of 208 CHC patients from Hospital Virgen de la Salud (Toledo, Spain) enrolled between 2008 and 2016, as previously described [ 30 ]. The study was performed according to the 1975 Declaration of Helsinki, and the Research Ethics Committee of the Hospital Virgen de la Salud approved it (CEIC/2013/32).…”

Section: Methodsmentioning

confidence: 99%

“…A GLM with binomial distribution was used to analyze cirrhosis progression, which provides the odds ratio (OR). GLM tests were adjusted by the most relevant covariables selected by a stepwise algorithm ( p -value < 0.20 at each step) from the following list of variables: age, gender, time since HCV diagnosis, diabetes, injection drug use, high alcohol intake, time of follow-up, baseline LSM, HCV treatment (before and after starting the study among non-responder patients), HCV genotype, and other significant SNPs previously analyzed in this cohort (MERTK rs4374383 [ 37 ], PNPLA3 rs738409 [ 38 ], IL7RA rs6897932 [ 35 ], MTHFR rs1801133 [ 39 ], and DARC rs12075 [ 30 ]).…”

Section: Methodsmentioning

confidence: 99%

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TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

Resino

Fernández‐Rodríguez

Pineda‐Tenor³

et al. 2021

JCM

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Background: TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. Methods: We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. Results: The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). Conclusions: TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.

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Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study

Cited by 7 publications

References 48 publications

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

Relationship between Duffy Antigen Receptor for Chemokines and Clinical Characteristics in Han People with Chronic Hepatitis C Infection in Dalian, China

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

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