Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease.
OBJECTIVE
Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C→T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype.


METHODS
In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed.


RESULTS
At multivariate logistic regression analysis in the entire NAFLD cohort, the presence of significant liver fibrosis (>F1) was independently linked to high HOMA (OR 1.12, 95% CI 1.01-1.23, p = 0.02), NAFLD activity score ≥ 5 (OR 4.09, 95% CI 2.45-6.81, p<0.001), and GCKR C>T SNP (OR 2.06, 95% CI 1.43-2.98, p<0.001). Similar results were observed considering separately the two different NAFLD cohorts. GCKR C>T SNP was also associated with higher serum triglycerides (ANOVA, p = 0.02) in the entire cohort.


CONCLUSIONS
In patients with NAFLD, GCKR rs780094 C>T is associated with the severity of liver fibrosis and with higher serum triglyceride levels.
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Salvatore
S
Petta
Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Luca
L
Miele
Division of Gastroenterology, Dept. of Medical Sciences, University of Turin, Turin, Italy.
Elisabetta
E
Bugianesi
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Calogero
C
Cammà
Division of Gastroenterology, Dept. of Medical Sciences, University of Turin, Turin, Italy.
Chiara
C
Rosso
Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Stefania
S
Boccia
Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
Daniela
D
Cabibi
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Vito
V
Di Marco
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Stefania
S
Grimaudo
Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Antonio
A
Grieco
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Rosaria Maria
RM
Pipitone
Dipartimento di Medicina e Gastroenterologia, "Alma Mater Studiorum," Università di Bologna, Bologna, Italy.
Giulio
G
Marchesini
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Antonio
A
Craxì
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008049:Lipase / Q000235:genetics; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012802:Sicily; D014280:Triglycerides / Q000097:blood; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D048868:Adaptor Proteins, Signal Transducing; D008049:Lipase; D008565:Membrane Proteins; D014280:Triglycerides; C485100:GCKR protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent