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Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C.
Hepatology. 2011 Mar; 53(3):791-9.Hep

Abstract

Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P < 0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95% CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95% CI 1.3-3.6; P = 0.002), independently of confounders.

CONCLUSION

The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.

Authors+Show Affiliations

Department of Internal Medicine, Università degli Studi, Fondazione IRCCS Ospedale Maggiore Policlinico "Ca' Granda" IRCCS, Milan, Italy. luca.valenti@unimi.itNo 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

21319195

Citation

Valenti, Luca, et al. "Patatin-like Phospholipase Domain-containing 3 I148M Polymorphism, Steatosis, and Liver Damage in Chronic Hepatitis C." Hepatology (Baltimore, Md.), vol. 53, no. 3, 2011, pp. 791-9.
Valenti L, Rumi M, Galmozzi E, et al. Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology. 2011;53(3):791-9.
Valenti, L., Rumi, M., Galmozzi, E., Aghemo, A., Del Menico, B., De Nicola, S., Dongiovanni, P., Maggioni, M., Fracanzani, A. L., Rametta, R., Colombo, M., & Fargion, S. (2011). Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology (Baltimore, Md.), 53(3), 791-9. https://doi.org/10.1002/hep.24123
Valenti L, et al. Patatin-like Phospholipase Domain-containing 3 I148M Polymorphism, Steatosis, and Liver Damage in Chronic Hepatitis C. Hepatology. 2011;53(3):791-9. PubMed PMID: 21319195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. AU - Valenti,Luca, AU - Rumi,Mariagrazia, AU - Galmozzi,Enrico, AU - Aghemo,Alessio, AU - Del Menico,Benedetta, AU - De Nicola,Stella, AU - Dongiovanni,Paola, AU - Maggioni,Marco, AU - Fracanzani,Anna Ludovica, AU - Rametta,Raffaela, AU - Colombo,Massimo, AU - Fargion,Silvia, Y1 - 2011/02/11/ PY - 2010/10/09/received PY - 2010/11/18/accepted PY - 2011/2/15/entrez PY - 2011/2/15/pubmed PY - 2011/5/13/medline SP - 791 EP - 9 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 53 IS - 3 N2 - UNLABELLED: Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P < 0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95% CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95% CI 1.3-3.6; P = 0.002), independently of confounders. CONCLUSION: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/21319195/Patatin_like_phospholipase_domain_containing_3_I148M_polymorphism_steatosis_and_liver_damage_in_chronic_hepatitis_C_ L2 - https://doi.org/10.1002/hep.24123 DB - PRIME DP - Unbound Medicine ER -