Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis.
BACKGROUND
Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD).


METHODS
In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features.


RESULTS
IL-6 -174C variant was more prevalent (p<0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p<0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p<0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p<0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p=0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics.


CONCLUSIONS
Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.
Carulli
L
L
Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Nuvo Ospedale Civile S.Agostino-Estense, Via Giardini 1355, 41100 Modena, Italy. lucia.carulli@unimore.it
Canedi
I
I
Rondinella
S
S
Lombardini
S
S
Ganazzi
D
D
Fargion
S
S
De Palma
M
M
Lonardo
A
A
Ricchi
M
M
Bertolotti
M
M
Carulli
N
N
Loria
P
P
D016022:Case-Control Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D015850:Interleukin-6