scholarly journals SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis

2019 ◽  
Vol 28 (3) ◽  
pp. 297-302 ◽  
Author(s):  
Viktorija Basyte-Bacevice ◽  
Jurgita Skieceviciene ◽  
Irena Valantiene ◽  
Jolanta Sumskiene ◽  
Vitalija Petrenkiene ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
P Value ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Reduced Risk

Background & Aims: Two single nucleotide polymorphisms (SNPs) in SERPINA1 (Pi*Z rs28929474 and Pi*Srs17580) are risk factors for developing liver cirrhosis. A recent study identified a common SNP in HSD17B13(rs72613567) that conferred protection from chronic liver disease. The aim of the present study was to testthese associations in a cohort of Lithuanian patients with liver fibrosis or cirrhosis. Methods: The study included 302 patients with cirrhosis, 127 patients with liver fibrosis (METAVIR stagesI-III) and 548 controls, all from Lithuania. SNPs were genotyped by quantitative PCR, using TaqMan allelicdiscrimination assays. Adjusted p value of ≤ 0.016 was considered significant. Results: Genotype distributions of SERPINA1 and HSD17B13 SNPs were in Hardy-Weinberg equilibrium.SERPINA1 Pi*Z was not associated with liver fibrosis or cirrhosis. HSD17B13 rs10433937 (in high linkagedisequilibrium with rs72613567; r 2 =0.96) also showed no overall association with liver disease, but the GG-genotype was associated with reduced risk of liver fibrosis (aOR 0.37, p=0.03). SERPINA1 Pi*S was associatedwith higher risk of developing hepatic fibrosis (aOR 3.42, p=0.001) and cirrhosis (aOR 2.59, p=0.02). Conclusions: We found that SERPINA1 Pi*S variant conferred an increased risk of developing liver fibrosis,while SERPINA1 Pi*Z and HSD17B13 rs10433937 were not associated with liver fibrosis or cirrhosis ofdifferent aetiology.

HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3310-3315 ◽  
Author(s):  
Marijke Niens ◽  
Ruth F. Jarrett ◽  
Bouke Hepkema ◽  
Ilja M. Nolte ◽  
Arjan Diepstra ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Hla Class I ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Barr Virus ◽  
Increased Risk ◽  
Peptide Binding Groove ◽  
Epstein Barr ◽  
Binding Groove ◽  
Reduced Risk

AbstractPrevious studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)–positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV− HL, and 59 control participants. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV− HL. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02–specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV− HL. The percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV− HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV+ HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.

scholarly journals PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Massarenti ◽  
Christian Enevold ◽  
Dres Damgaard ◽  
Niels Ødum ◽  
Peter Garred ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Smoking Status ◽  
Nucleotide Polymorphisms ◽  
Regression Analyses ◽  
Post Translational Modification ◽  
Pathogenic Role ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Citrullinated Protein ◽  
Reduced Risk

Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The HLA-DRB1 locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in PADI4 (OR: 0.82, p=0.04). rs74058715(T) in PADI4 conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In HLA-DRB1*04-positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of PADI4 rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of PADI4 rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and HLA-DRB1*04 (p=0.004 and p=0.008, respectively) Thus, PADI4 polymorphisms associate with ACPA-positive RA, particularly in HLA-DRB1*04-positive individuals, and with ACPA-negative RA independently of HLA-DRB1*04.

scholarly journals A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247277
Author(s):  
Alec T. McIntosh ◽  
Renhuizi Wei ◽  
Jaeil Ahn ◽  
Brad E. Aouizerat ◽  
Seble G. Kassaye ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Pharmacological Intervention ◽  
Genetic Associations ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Hiv Coinfection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Genomic Variant

HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women’s Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.

scholarly journals A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women

2020 ◽  
Author(s):  
Alec T McIntosh ◽  
Renhuizi Wei ◽  
Jaeil Ahn ◽  
Brad E Aouizerat ◽  
Seble G Kassaye ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Pharmacological Intervention ◽  
Genetic Associations ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Hiv Coinfection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Genomic Variant

HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.

scholarly journals TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis

2019 ◽  
Vol 20 (6) ◽  
pp. 1277 ◽  
Author(s):  
Viktorija Basyte-Bacevice ◽  
Jurgita Skieceviciene ◽  
Irena Valantiene ◽  
Jolanta Sumskiene ◽  
Vitalija Petrenkiene ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Large Scale ◽  
European Population ◽  
Eastern European ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver

Previous large-scale genetic studies identified single nucleotide polymorphisms (SNPs) of the TM6SF2 and MBOAT7 genes as risk factors for alcoholic liver cirrhosis and non-alcoholic fatty liver disease. In this study, we tried to evaluate the association between TM6SF2 variant rs58542926 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis of different etiology. In parallel, we also aimed to evaluate whether these two SNPs modify the effects of the PNPLA3 rs738409 risk variant for the development of hepatic fibrosis and liver cirrhosis. The study was conducted at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, and included 334 patients with liver cirrhosis, 128 patients with liver fibrosis, and 550 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, TM6SF2 rs58542926 as well as MBOAT7 rs641738 were not linked to hepatic fibrosis, alcohol or hepatitis C virus induced liver cirrhosis in an Eastern European population. These genetic variations also did not mediate the effect of PNPLA3 rs738409 SNP for liver developing liver fibrosis or liver cirrhosis.

scholarly journals Genetic Factors Associated with COPD Depend on the Ancestral Caucasian/Amerindian Component in the Mexican Population

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 599
Author(s):  
Gloria Pérez-Rubio ◽  
Ramcés Falfán-Valencia ◽  
Juan Carlos Fernández-López ◽  
Alejandra Ramírez-Venegas ◽  
Rafael de Jesús Hernández-Zenteno ◽  
...  
Keyword(s):  
Lower Risk ◽  
Genetic Factors ◽  
Principal Component ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotyping Array ◽  
Mexican Mestizo ◽  
Factors Associated ◽  
Increased Risk ◽  
Reduced Risk

Genetic variability influences the susceptibility to and severity of complex diseases; there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects; 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes; however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD; individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD.

scholarly journals Portal vein thrombosis in patients with liver cirrhosis: Risk factors and clinical presentation

2021 ◽  
Author(s):  
Sondes Bizid ◽  
Houssaina Jlassi ◽  
Maroua Ben Abbes ◽  
Ghanem Mohamed ◽  
Hela Ghedira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Anticoagulation Therapy ◽  
Factor V Leiden ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
Increased Risk

Abstract Background:Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. PVT impact on disease progression is not clarified as yet. Anticoagulation therapy is considered effective in this setting, but is associated with potentially bleeding episodes. Aim : to assess the risk factors and clinical impact of non-neoplastic PVT complicating cirrhosis, as well as the treatment profile and its efficacy in clinical practice.Methods:A retrospective monocentric study over a period of 19 years including all patients diagnosed with cirrhosis and non-neoplastic PVT was conducted.Results:A total of 49 patients were enrolled in the present study.The mean age was 60.86±11.61 years old. Chronic viral hepatitis was the most frequent cause of cirrhosis (63.2%). Most of our cases had advanced liver disease (89.9% Child class B/C) with a mean MELD score of 19.27. The risk factors for thrombophilia, inherited or acquired, were: a deficiency in coagulation inhibitors, either isolated or combined (protein S, protein C and antithrombin III) in 19 patients, a heterozygous Factor V Leiden mutation in 2 patients, a heterozygous MTHFR mutation in one patient, an antiphospholipid antibodies syndrome in 2 patients, an essential thrombocythemia in one patient. Anticoagulant therapy was indicated in half of the cases. Multivariate analyses demonstrated that thrombus extension was the only independent predictive factor of portal vein recanalization (p=0.009). During follow-up, progression was observed in 8% of treated patients with anticoagulants versus 12.5% of untreated patients (p=0.12). Our study has shown that anticoagulant treatment is not associated with elevated risk of bleeding or developing other complications. The mean survival was higher in patients treated successfully (38.31 months Vs 23.41 months, p=0.204). Conclusions:Our outcomes confirm that anticoagulation therapy in cirrhotic patients with non-neoplastic PVT is not associated with increased risk of liver disease decompensation, including bleeding.

scholarly journals Impacts of single nucleotide polymorphisms in three microRNAs (miR-146a, miR-196a2 and miR-499) on the susceptibility to cervical cancer among Indian women

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Nisha Thakur ◽  
Pallavi Singhal ◽  
Ravi Mehrotra ◽  
Mausumi Bharadwaj
Keyword(s):  
Cervical Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Susceptibility ◽  
Hpv Infection ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hpv Dna ◽  
Cervical Cancer Risk ◽  
Increased Risk

Abstract Background: Cervical cancer is the second major female cancer in India and constitutes one-fourth of the world’s burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in microRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers. Objective: To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913), and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population. Methods: Three hundred samples were genotyped by Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA. Results: In this case–control study, 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [odds ratio (OR) (95% confidence interval (CI)) = 0.81 (0.57–1.14), P-value = 0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR (95% CI) = 0.36 (0.26–0.50), P-value<0.0001]. Approximately 1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR (95% CI) = 1.22 (0.63–2.36), P-value = 0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [P<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [P<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend toward higher cervical cancer risk [OR > 1.00, P>0.05]. Conclusion: Polymorphisms in miR-146a, miR-196a2, and miR-499 individually or collectively have the prospective to emerge as biomarkers for cervical cancer.

Sign in / Sign up

Export Citation Format

Share Document