title: Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients.
abstract: OBJECTIVE
  To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients.
  
  
  METHODS
  We performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F ≥3 and FIB-4 ≥3.25), rapid fibrosis progression (FPR ≥0.10 fibrosis units/year), severe activity grade (A≥3), and steatosis (fatty hepatocytes ≥10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables.
  
  
  RESULTS
  Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P = 0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P = 0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P = 0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval = 1.11; 69.0; P = 0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P = 0.054). Finally, we did not find any association for A at least 3 and liver steatosis.
  
  
  CONCLUSIONS
  PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients.
authors.affiliation: aUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda bUnidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón" cInstituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: Mónica
authors.initials: M
authors.lastname: Gutierrez-Rivas
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.forename: Francisco
authors.initials: F
authors.lastname: Tejerina
authors.forename: Cristina
authors.initials: C
authors.lastname: Diez
authors.forename: Sonia
authors.initials: S
authors.lastname: Vázquez-Morón
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D001706:Biopsy; D060085:Coinfection / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000473:pathology*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent