7 results on '"Ansari, M. Azim"'
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2. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- Author
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Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U., Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Matthias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Corradini, Stefano Ginanni, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, Stickel, Felix, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U., Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Matthias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Corradini, Stefano Ginanni, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix
- Abstract
Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. - Design: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). - Results: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10⁻⁹, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10⁻⁵, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10⁻⁴⁴). - Conclusion: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
- Published
- 2022
3. Genetic variation in modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.
- Author
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UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, Stickel, Felix, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix
- Abstract
Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Associations with variants rs738409 in and rs58542926 in previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in was associated with an increased leucocyte telomere length (p=2.12×10). This study identifies rs2242652 in as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
- Published
- 2022
4. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- Author
-
Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U., Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Matthias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Corradini, Stefano Ginanni, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, Stickel, Felix, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U., Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Matthias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Corradini, Stefano Ginanni, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix
- Abstract
Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. - Design: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). - Results: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10⁻⁹, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10⁻⁵, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10⁻⁴⁴). - Conclusion: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
- Published
- 2022
5. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis.
- Author
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UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Innes, Hamish, Nischalke, Hans Dieter, Guha, Indra Neil, Weiss, Karl Heinz, Irving, Will, Gotthardt, Daniel, Barnes, Eleanor, Fischer, Janett, Ansari, M Azim, Rosendahl, Jonas, Lin, Shang-Kuan, Marot, Astrid, Pedergnana, Vincent, Casper, Markus, Benselin, Jennifer, Lammert, Frank, McLauchlan, John, Lutz, Philip L, Hamill, Victoria, Mueller, Sebastian, Morling, Joanne R, Semmler, Georg, Eyer, Florian, von Felden, Johann, Link, Alexander, Vogel, Arndt, Marquardt, Jens U, Sulk, Stefan, Trebicka, Jonel, Valenti, Luca, Datz, Christian, Reiberger, Thomas, Schafmayer, Clemens, Berg, Thomas, Deltenre, Pierre, Hampe, Jochen, Stickel, Felix, Buch, Stephan, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Innes, Hamish, Nischalke, Hans Dieter, Guha, Indra Neil, Weiss, Karl Heinz, Irving, Will, Gotthardt, Daniel, Barnes, Eleanor, Fischer, Janett, Ansari, M Azim, Rosendahl, Jonas, Lin, Shang-Kuan, Marot, Astrid, Pedergnana, Vincent, Casper, Markus, Benselin, Jennifer, Lammert, Frank, McLauchlan, John, Lutz, Philip L, Hamill, Victoria, Mueller, Sebastian, Morling, Joanne R, Semmler, Georg, Eyer, Florian, von Felden, Johann, Link, Alexander, Vogel, Arndt, Marquardt, Jens U, Sulk, Stefan, Trebicka, Jonel, Valenti, Luca, Datz, Christian, Reiberger, Thomas, Schafmayer, Clemens, Berg, Thomas, Deltenre, Pierre, Hampe, Jochen, Stickel, Felix, and Buch, Stephan
- Abstract
The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an in
- Published
- 2021
6. Global prevalence and phylogeny of hepatitis B virus (HBV) drug and vaccine resistance mutations.
- Author
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Mokaya, Jolynne, Mokaya, Jolynne, Vasylyeva, Tetyana I, Barnes, Eleanor, Ansari, M Azim, Pybus, Oliver G, Matthews, Philippa C, Mokaya, Jolynne, Mokaya, Jolynne, Vasylyeva, Tetyana I, Barnes, Eleanor, Ansari, M Azim, Pybus, Oliver G, and Matthews, Philippa C
- Abstract
Vaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations. We analysed sequences downloaded from the HBV Database and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution and estimated the age of selected mutations across tree branches. RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our data set, and a significantly higher rate in genotype C at 5.4% (60/1102, p = 0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p = 0.002) and 1.6% (34/2109; p = 0.009), respectively. Phylogenetic analysis suggested that RAM/VEMs can arise independently of treatment/vaccine exposure. In conclusion, HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C. Screening for genotype and for resistance-associated mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.
- Published
- 2021
7. Simultaneous Viral Whole-Genome Sequencing and Differential Expression Profiling in Respiratory Syncytial Virus Infection of Infants
- Author
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CTI Bont, Infectiezieken, Infectieziekten onderzoek1 (Bont), Child Health, Infection & Immunity, Lin, Gu-Lung, Golubchik, Tanya, Drysdale, Simon, O'Connor, Daniel, Jefferies, Kimberley, Brown, Anthony, de Cesare, Mariateresa, Bonsall, David, Ansari, M Azim, Aerssens, Jeroen, Bont, Louis, Openshaw, Peter, Martinón-Torres, Federico, Bowden, Rory, Pollard, Andrew J, CTI Bont, Infectiezieken, Infectieziekten onderzoek1 (Bont), Child Health, Infection & Immunity, Lin, Gu-Lung, Golubchik, Tanya, Drysdale, Simon, O'Connor, Daniel, Jefferies, Kimberley, Brown, Anthony, de Cesare, Mariateresa, Bonsall, David, Ansari, M Azim, Aerssens, Jeroen, Bont, Louis, Openshaw, Peter, Martinón-Torres, Federico, Bowden, Rory, and Pollard, Andrew J
- Published
- 2020
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