Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women

M. Sarkar, B. Aouzierat, P. Bacchetti, L. Prokunina-Olsson, A. French, E. Seaberg, T. R. O'Brien, M. H. Kuniholm, H. Minkoff, M. Plankey, Howard Strickler, M. G. Peters

Research output: Contribution to journalArticle

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Abstract

African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/HCV-coinfected women followed in the multicentre, NIH-funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14-0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45-0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16-1.04, P = 0.060 and HR 0.78, 95% CI 0.51-1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality.

Original languageEnglish (US)
Pages (from-to)1055-1060
Number of pages6
JournalJournal of Viral Hepatitis
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Hepacivirus
HIV
Mortality
Liver
African Americans
Genotype
Behavioral Genetics
Genetic Models
Genetic Polymorphisms
Hispanic Americans
Self Report
Cohort Studies
Genes

Keywords

  • death
  • ethnicity
  • genetic, interferon-λ
  • polymorphisms

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Sarkar, M., Aouzierat, B., Bacchetti, P., Prokunina-Olsson, L., French, A., Seaberg, E., ... Peters, M. G. (2015). Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women. Journal of Viral Hepatitis, 22(12), 1055-1060. https://doi.org/10.1111/jvh.12431

Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women. / Sarkar, M.; Aouzierat, B.; Bacchetti, P.; Prokunina-Olsson, L.; French, A.; Seaberg, E.; O'Brien, T. R.; Kuniholm, M. H.; Minkoff, H.; Plankey, M.; Strickler, Howard; Peters, M. G.

In: Journal of Viral Hepatitis, Vol. 22, No. 12, 01.12.2015, p. 1055-1060.

Research output: Contribution to journalArticle

Sarkar, M, Aouzierat, B, Bacchetti, P, Prokunina-Olsson, L, French, A, Seaberg, E, O'Brien, TR, Kuniholm, MH, Minkoff, H, Plankey, M, Strickler, H & Peters, MG 2015, 'Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women', Journal of Viral Hepatitis, vol. 22, no. 12, pp. 1055-1060. https://doi.org/10.1111/jvh.12431
Sarkar, M. ; Aouzierat, B. ; Bacchetti, P. ; Prokunina-Olsson, L. ; French, A. ; Seaberg, E. ; O'Brien, T. R. ; Kuniholm, M. H. ; Minkoff, H. ; Plankey, M. ; Strickler, Howard ; Peters, M. G. / Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women. In: Journal of Viral Hepatitis. 2015 ; Vol. 22, No. 12. pp. 1055-1060.
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abstract = "African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/HCV-coinfected women followed in the multicentre, NIH-funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95{\%} CI 0.14-0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95{\%} CI 0.45-0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95{\%} CI 0.16-1.04, P = 0.060 and HR 0.78, 95{\%} CI 0.51-1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality.",
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