A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.
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...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2021-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0247277 |
id |
doaj-76f5d8eaaeba46409350200295f520aa |
---|---|
record_format |
Article |
spelling |
doaj-76f5d8eaaeba46409350200295f520aa2021-07-13T04:31:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01163e024727710.1371/journal.pone.0247277A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.Alec T McIntoshRenhuizi WeiJaeil AhnBrad E AouizeratSeble G KassayeMichael H AugenbraunJennifer C PriceAudrey L FrenchStephen J GangeKathryn M AnastosRadoslav GoldmanHIV 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.https://doi.org/10.1371/journal.pone.0247277 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alec T McIntosh Renhuizi Wei Jaeil Ahn Brad E Aouizerat Seble G Kassaye Michael H Augenbraun Jennifer C Price Audrey L French Stephen J Gange Kathryn M Anastos Radoslav Goldman |
spellingShingle |
Alec T McIntosh Renhuizi Wei Jaeil Ahn Brad E Aouizerat Seble G Kassaye Michael H Augenbraun Jennifer C Price Audrey L French Stephen J Gange Kathryn M Anastos Radoslav Goldman A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. PLoS ONE |
author_facet |
Alec T McIntosh Renhuizi Wei Jaeil Ahn Brad E Aouizerat Seble G Kassaye Michael H Augenbraun Jennifer C Price Audrey L French Stephen J Gange Kathryn M Anastos Radoslav Goldman |
author_sort |
Alec T McIntosh |
title |
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. |
title_short |
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. |
title_full |
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. |
title_fullStr |
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. |
title_full_unstemmed |
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. |
title_sort |
genomic variant of alpk2 is associated with increased liver fibrosis risk in hiv/hcv coinfected women. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2021-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0247277 |
work_keys_str_mv |
AT alectmcintosh agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT renhuiziwei agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT jaeilahn agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT bradeaouizerat agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT seblegkassaye agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT michaelhaugenbraun agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT jennifercprice agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT audreylfrench agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT stephenjgange agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT kathrynmanastos agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT radoslavgoldman agenomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT alectmcintosh genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT renhuiziwei genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT jaeilahn genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT bradeaouizerat genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT seblegkassaye genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT michaelhaugenbraun genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT jennifercprice genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT audreylfrench genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT stephenjgange genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT kathrynmanastos genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen AT radoslavgoldman genomicvariantofalpk2isassociatedwithincreasedliverfibrosisriskinhivhcvcoinfectedwomen |
_version_ |
1721306250959912960 |