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Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C.
Hepatology. 2011 Jul; 54(1):60-9.Hep

Abstract

Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08-6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50-6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22-5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46-2.49, P = 0.875) and did not influence clinical or biological variables.

CONCLUSION

The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage.

Authors+Show Affiliations

Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme Hospital, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21488075

Citation

Trépo, Eric, et al. "Impact of Patatin-like Phospholipase-3 (rs738409 C>G) Polymorphism On Fibrosis Progression and Steatosis in Chronic Hepatitis C." Hepatology (Baltimore, Md.), vol. 54, no. 1, 2011, pp. 60-9.
Trépo E, Pradat P, Potthoff A, et al. Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology. 2011;54(1):60-9.
Trépo, E., Pradat, P., Potthoff, A., Momozawa, Y., Quertinmont, E., Gustot, T., Lemmers, A., Berthillon, P., Amininejad, L., Chevallier, M., Schlué, J., Kreipe, H., Devière, J., Manns, M., Trépo, C., Sninsky, J., Wedemeyer, H., Franchimont, D., & Moreno, C. (2011). Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology (Baltimore, Md.), 54(1), 60-9. https://doi.org/10.1002/hep.24350
Trépo E, et al. Impact of Patatin-like Phospholipase-3 (rs738409 C>G) Polymorphism On Fibrosis Progression and Steatosis in Chronic Hepatitis C. Hepatology. 2011;54(1):60-9. PubMed PMID: 21488075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. AU - Trépo,Eric, AU - Pradat,Pierre, AU - Potthoff,Andrej, AU - Momozawa,Yukihide, AU - Quertinmont,Eric, AU - Gustot,Thierry, AU - Lemmers,Arnaud, AU - Berthillon,Pascale, AU - Amininejad,Leila, AU - Chevallier,Michéle, AU - Schlué,Jerome, AU - Kreipe,Hans, AU - Devière,Jacques, AU - Manns,Michael, AU - Trépo,Christian, AU - Sninsky,John, AU - Wedemeyer,Heiner, AU - Franchimont,Denis, AU - Moreno,Christophe, PY - 2011/4/14/entrez PY - 2011/4/14/pubmed PY - 2011/10/1/medline SP - 60 EP - 9 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 54 IS - 1 N2 - UNLABELLED: Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08-6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50-6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22-5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46-2.49, P = 0.875) and did not influence clinical or biological variables. CONCLUSION: The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/21488075/Impact_of_patatin_like_phospholipase_3__rs738409_C>G__polymorphism_on_fibrosis_progression_and_steatosis_in_chronic_hepatitis_C_ L2 - https://doi.org/10.1002/hep.24350 DB - PRIME DP - Unbound Medicine ER -