Abstract
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.
Original language | English (US) |
---|---|
Article number | e0247277 |
Journal | PloS one |
Volume | 16 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2021 |
Keywords
- Adult
- Alleles
- Biomarkers
- Coinfection
- Female
- Gene Frequency/genetics
- Genomics
- HIV Infections/complications
- HIV-1/pathogenicity
- Hepacivirus/pathogenicity
- Hepatitis C/complications
- Humans
- Liver/pathology
- Liver Cirrhosis/genetics
- Middle Aged
- Platelet Count
- Protein Kinases/genetics
- Risk Factors
- United States/epidemiology
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General
- General Biochemistry, Genetics and Molecular Biology