IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease.
OBJECTIVE
Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients.


METHODS
One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested.


RESULTS
Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorphism, compared with 72 (45%) and 14 (8.8%) with TC and TT variants, respectively. PNPLA3 rs738409 CC polymorphism was present in 47 (29.4%) patients, compared with 79 (49.4%) and 34 (21.3%) with CG and GG variants, respectively. Multivariate logistic regression analysis showed that age (OR 1.043, 95% CI 1.012-1.075, p=0.007), triglycerides (OR 1.005, 95% CI 1.000-1.010, p=0.04), hyperuricemia (OR 5.027, 95% CI 1.839-13.742, p=0.002), IL28B rs12979860 TT/TC (OR 0.219, 95% CI 0.101-0.472, p<0.001), and steatosis grade (OR 1.704, 95% CI 1.048-2.773, p=0.03) were independently linked to moderate-severe lobular inflammation. Finally, IL28B rs12979860 CC was associated with severe fibrosis (F3-F4) on univariate analysis, even if only older age (OR 1.064, 95% CI 1.026-1.104, p=0.001), high HOMA (OR 1.213, 95% CI 1.068-1.377, p=0.003), and lobular inflammation (OR 3.181, 95% CI 1.438-7.036, p=0.004), remained associated in multivariate logistic regression analysis.


CONCLUSIONS
In NAFLD patients, IL28B rs12979860 CC genotype, together with PNPLA3 rs738409 GG, is associated with the severity of liver damage.
Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Italy. petsa@inwind.it
Salvatore
S
Petta
Stefania
S
Grimaudo
Calogero
C
Cammà
Daniela
D
Cabibi
Vito
V
Di Marco
Giusalba
G
Licata
Rosaria Maria
RM
Pipitone
Antonio
A
Craxì
D000328:Adult; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D020641:Polymorphism, Single Nucleotide; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent