The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP).
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.
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Anita
A
Arslanow
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Caroline S
CS
Stokes
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Susanne N
SN
Weber
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Frank
F
Grünhage
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Frank
F
Lammert
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.
Marcin
M
Krawczyk
D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D054459:Elasticity Imaging Techniques; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
TM6SF2; adiponutrin; elastography; non-alcoholic fatty liver disease