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

• Published in: PloS one Vol. 16; no. 3; p. e0247277
• Main Authors: McIntosh, Alec T, Wei, Renhuizi, Ahn, Jaeil, Aouizerat, Brad E, Kassaye, Seble G, Augenbraun, Michael H, Price, Jennifer C, French, Audrey L, Gange, Stephen J, Anastos, Kathryn M, Goldman, Radoslav
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11-03-2021; Public Library of Science (PLoS)
• Subjects: Adult; Alleles; Antibodies; Antiretroviral agents; Biochemistry; Bioinformatics; Biology and Life Sciences; Biomarkers; Chronic infection; Coinfection; Comorbidity; Complications and side effects; Data analysis; Dentistry; Editing; Enzymes; Epidemiology; Ethnicity; Experimentation; Female; Fibrosis; Gene Frequency - genetics; Genetic aspects; Genetic variation; Genomes; Genomics; Genotype & phenotype; Health aspects; Health care facilities; Health risk assessment; Health risks; Hepacivirus - pathogenicity; Hepatitis C; Hepatitis C - complications; Hepatitis C - genetics; Highly active antiretroviral therapy; Hispanic people; HIV; HIV infection; HIV Infections - complications; HIV Infections - genetics; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Liver; Liver - pathology; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - virology; Liver diseases; Medical research; Medicine; Medicine and Health Sciences; Medicine, Experimental; Methodology; Middle Aged; Minority & ethnic groups; Oncology; Pathogenesis; Platelet Count; Principal components analysis; Protein Kinases - genetics; Protein Kinases - metabolism; Proteins; Public health; Research facilities; Review boards; Risk analysis; Risk Factors; Supervision; United States - epidemiology; Viruses; Visualization; Women; Womens health; United States; Cook County Illinois; Los Angeles California; New York; San Francisco California; United States > US; California; Chicago Illinois; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0247277

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.