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The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP).
Liver Int 2016; 36(3):418-26LI

Abstract

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disorder. The PNPLA3 (adiponutrin) variant p.I148M has been identified as common genetic modifier of NAFLD. Our aim was to assess the relationships between genetic risk and non-invasively measured liver fat content.

METHODS

Hepatic steatosis was quantified by transient elastography, using the controlled attenuation parameter (CAP) in 174 patients with chronic liver diseases (50% women, age 18-77 years). In addition, a cohort of 174 gender-matched healthy controls (50% women, age 32-77 years) was recruited. The PNPLA3 mutation as well as the novel NAFLD-predisposing genetic variant (TM6SF2 p.E167K) were genotyped with allele-specific probes.

RESULTS

The PNPLA3 genotype correlated significantly (P = 0.001) with hepatic CAP measurements. The p.148M risk allele increased the odds of developing liver steatosis (OR = 2.39, P = 0.023). In multivariate models, BMI and PNPLA3 mutation were both independently associated with CAP values (P < 0.001 and P = 0.007, respectively). Carriers of the TM6SF2 risk allele presented with increased aminotransferase activities (ALT: P = 0.007, AST: P = 0.004), but the presence of this variant did not affect CAP values.

CONCLUSIONS

The PNPLA3 p.I148M variant represents the most important prosteatotic genetic risk factor. NAFLD carriers of this variant should be followed up carefully, with elastography and CAP being ideally suited for this purpose.

Authors+Show Affiliations

Department of Medicine II, Saarland University Medical Center, Homburg, Germany.Department of Medicine II, Saarland University Medical Center, Homburg, Germany.Department of Medicine II, Saarland University Medical Center, Homburg, Germany.Department of Medicine II, Saarland University Medical Center, Homburg, Germany.Department of Medicine II, Saarland University Medical Center, Homburg, Germany.Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Pub Type(s)

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

Language

eng

PubMed ID

26264356

Citation

Arslanow, Anita, et al. "The Common PNPLA3 Variant p.I148M Is Associated With Liver Fat Contents as Quantified By Controlled Attenuation Parameter (CAP)." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 36, no. 3, 2016, pp. 418-26.
Arslanow A, Stokes CS, Weber SN, et al. The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). Liver Int. 2016;36(3):418-26.
Arslanow, A., Stokes, C. S., Weber, S. N., Grünhage, F., Lammert, F., & Krawczyk, M. (2016). The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). Liver International : Official Journal of the International Association for the Study of the Liver, 36(3), pp. 418-26. doi:10.1111/liv.12937.
Arslanow A, et al. The Common PNPLA3 Variant p.I148M Is Associated With Liver Fat Contents as Quantified By Controlled Attenuation Parameter (CAP). Liver Int. 2016;36(3):418-26. PubMed PMID: 26264356.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). AU - Arslanow,Anita, AU - Stokes,Caroline S, AU - Weber,Susanne N, AU - Grünhage,Frank, AU - Lammert,Frank, AU - Krawczyk,Marcin, Y1 - 2015/10/03/ PY - 2015/04/29/received PY - 2015/08/07/accepted PY - 2015/8/13/entrez PY - 2015/8/13/pubmed PY - 2016/12/15/medline KW - TM6SF2 KW - adiponutrin KW - elastography KW - non-alcoholic fatty liver disease SP - 418 EP - 26 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int. VL - 36 IS - 3 N2 - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disorder. The PNPLA3 (adiponutrin) variant p.I148M has been identified as common genetic modifier of NAFLD. Our aim was to assess the relationships between genetic risk and non-invasively measured liver fat content. METHODS: Hepatic steatosis was quantified by transient elastography, using the controlled attenuation parameter (CAP) in 174 patients with chronic liver diseases (50% women, age 18-77 years). In addition, a cohort of 174 gender-matched healthy controls (50% women, age 32-77 years) was recruited. The PNPLA3 mutation as well as the novel NAFLD-predisposing genetic variant (TM6SF2 p.E167K) were genotyped with allele-specific probes. RESULTS: The PNPLA3 genotype correlated significantly (P = 0.001) with hepatic CAP measurements. The p.148M risk allele increased the odds of developing liver steatosis (OR = 2.39, P = 0.023). In multivariate models, BMI and PNPLA3 mutation were both independently associated with CAP values (P < 0.001 and P = 0.007, respectively). Carriers of the TM6SF2 risk allele presented with increased aminotransferase activities (ALT: P = 0.007, AST: P = 0.004), but the presence of this variant did not affect CAP values. CONCLUSIONS: The PNPLA3 p.I148M variant represents the most important prosteatotic genetic risk factor. NAFLD carriers of this variant should be followed up carefully, with elastography and CAP being ideally suited for this purpose. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/26264356/The_common_PNPLA3_variant_p_I148M_is_associated_with_liver_fat_contents_as_quantified_by_controlled_attenuation_parameter__CAP__ L2 - https://doi.org/10.1111/liv.12937 DB - PRIME DP - Unbound Medicine ER -