IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease

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• 作者：Salvatore Petta¹ ; ^{petsa@inwind.it} ; Stefania Grimaudo¹ ; Calogero Camm&agrave ; ¹ ; Daniela Cabibi² ; Vito Di Marco¹ ; Giusalba Licata¹ ; Rosaria Maria Pipitone¹ ; Antonio Craxì ; ¹
• 关键词：IL28B ; interleukin 28B ; PNPLA3 ; patatin-like phospholipase-3 ; UA ; uric acid ; IR ; insulin resistance ; NAFLD ; non-alcoholic fatty liver disease ; NASH ; non-alcoholic steatohepatitis ; HOMA ; homeostasis model assessment
• 刊名：Journal of Hepatology
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：56
• 期：6
• 页码：1356-1362
• 全文大小：676 K

文摘

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Background & Aims

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.