PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes.
BACKGROUND
Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels.


METHODS
The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography.


RESULTS
Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001).


CONCLUSIONS
Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
*Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; †Division of Gastroenterology, Fondazione Tommaso Campanella, University Magna Graecia of Catanzaro, Catanzaro, Italy; ‡Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico, and DEPT, Università degli Studi di Milano, Milano, Italy; §Department of Medical and Surgical Sciences, Clinical Nutrition Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy; ‖University Magna Graecia of Catanzaro, Catanzaro, Italy; ¶Unit of Gastroenterology, Fondazione IRCCS Ca' Granda-Ospedale Policlinico Milano, Milan, Italy; **Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; and ††Cardiology Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
Rosellina Margherita
RM
Mancina
Rocco
R
Spagnuolo
Marta
M
Milano
Simona
S
Brogneri
Attilio
A
Morrone
Cristina
C
Cosco
Veronica
V
Lazzaro
Cristina
C
Russo
Yvelise
Y
Ferro
Piero
P
Pingitore
Arturo
A
Pujia
Tiziana
T
Montalcini
Patrizia
P
Doldo
Pietro
P
Garieri
Luca
L
Piodi
Flavio
F
Caprioli
Luca
L
Valenti
Stefano
S
Romeo
D000410:Alanine Transaminase / Q000097:blood*; D000483:Alleles; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000235:genetics; D007558:Italy; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent