Inducible nitric oxide synthase gene (NOS2A) haplotypes and the outcome of hepatitis C virus infection.
Inducible nitric oxide synthase (iNOS) is an important molecule involved in the host defense against infectious agents. iNOS is encoded by the NOS2A gene and well-defined haplotypes exist with respect to this gene. We examined whether these haplotypes were associated with the outcome of hepatitis C virus (HCV) infection in 619 Caucasian patients from seven European liver centres. We observed five major haplotypes: (-277A)+(-1026G)+(-1659C): haplotype 1; (-277G)+(-1026T)+(-1659C): haplotype 2; (-277G)+(-1026G)+(-1659C): haplotype 3; (-277G)+(-1026T)+(-1659T): haplotype 4; and (-277A)+(-1026T)+(-1659C): haplotype 5. Distributions of these haplotypes are comparable with those of previous studies. Homozygotes for haplotype 2 or those with haplotypes 2/4 were more likely than those with the 1/1 (wild type) combination to have self-limiting infections (odds ratios (OR)=3.43; 95% confidence intervals (95% CI): 1.10-8.0; P=0.0206 and OR=5.15; 95% CI: 1.32-14.32; P=0.0018, respectively). Conversely, carriage of haplotype 1 was associated with the lack of self-limiting disease (OR=0.48; 95% CI: 0.27-0.83; P=0.009). The effect was mainly among males (OR=0.41; 95% CI: 0.182-0.942; P=0.031 for males, and OR=0.55; 95% CI: 0.24-1.37; P=0.136 for women). Carriage of haplotype 1 was not associated with initial response (P=0.268) or sustained response (P>0.171). Combinations of haplotypes 1/4 were more likely to respond to interferon monotherapy in comparison of initial responders to nonresponders (OR=2.25; 95% CI: 1.05-5.68; P=0.0275).
Yee
L J
LJ
Hepatology Division, Imperial College Faculty of Medicine at St Mary's Hospital, London, UK. yeel@edc.pitt.edu
Knapp
S
S
Burgner
D
D
Hennig
B J W
BJ
Frodsham
A J
AJ
Wright
M
M
Thomas
H C
HC
Hill
A V S
AV
Thursz
M R
MR
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D006720:Homozygote; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D016017:Odds Ratio; D012189:Retrospective Studies; D014766:Viremia / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D044465:White People
D000998:Antiviral Agents; D016898:Interferon-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II