Stättermayer Albert F, Rutter Karoline, Beinhardt Sandra, Wrba Fritz, Scherzer Thomas-Matthias, Strasser Michael, Hofer Harald, Steindl-Munda Petra, Trauner Michael, Ferenci Peter
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
Liver Int. 2014 Mar;34(3):388-95. doi: 10.1111/liv.12269. Epub 2013 Jul 21.
In chronic hepatitis C (CHC), steatosis is associated with fibrosis and impaired response to antiviral therapy. Recently, a polymorphism of single nucleotide polymorphism SNP rs2645424 of farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified in NAFLD/NASH as a possible causal link to steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (PNPLA3) is a well described factor for steatosis. This study evaluated the relation of these SNPs on steatosis, fibrosis and treatment response in CHC.
The SNPs rs738409478 and rs2645424 were determined by real-time PCR in 478 patients with CHC (m/f: 314/164; mean age: 44.9 ± 10.7; GT1: 387, GT4: 91) who completed treatment with peg-IFN-α-2a/ribavirin. All had a pretreatment liver biopsy. Steatosis and fibrosis were graded by board-certified pathologists according to Brunt and METAVIR respectively.
The distribution of FDFT1 rs2645424 was GG: 186 (38.9%), AG: 222 (46.4%) and AA: 70 (14.6%) and of the rs738409 PNPLA3 allele: CC: 269 (56.3%), CG: 177 (37.0%) and GG: 32 (6.7%). Overall, FDTF1 polymorphism was not linked to the extent of steatosis or fibrosis. However, in patients without steatosis the AA genotype was associated with advanced fibrosis [AA: 8/20 (40.0%), AG: 6/70 (8.5%), GG: 9/57 (16.1%), P = 0.003]. In contrast, the minor PNPLA3 allele was associated with both steatosis and advanced fibrosis (P < 0.001). Both SNPs did not influence treatment response.
The minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic but not in the steatotic subgroup. This may reflect different metabolic pathways in fibrosis progression for steatotic and non-steatotic patients with CHC.
在慢性丙型肝炎（CHC）中，脂肪变性与纤维化及抗病毒治疗反应受损相关。最近，在非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NAFLD/NASH）中发现法尼基二磷酸法尼基转移酶1（FDFT1）的单核苷酸多态性SNP rs2645424的一种多态性可能是脂肪变性和纤维化进展的因果联系。脂肪营养素基因（PNPLA3）中的SNP rs738409是一个已充分描述的脂肪变性相关因素。本研究评估了这些单核苷酸多态性与CHC中脂肪变性、纤维化及治疗反应的关系。
通过实时聚合酶链反应（PCR）对478例完成聚乙二醇干扰素α-2a/利巴韦林治疗的CHC患者（男/女：314/164；平均年龄：44.9±10.7；基因1型：387例，基因4型：91例）测定SNP rs738409478和rs2645424。所有患者均进行了治疗前肝活检。脂肪变性和纤维化分别由经委员会认证的病理学家根据布伦特（Brunt）和梅塔维（METAVIR）标准进行分级。
FDFT1 rs2645424的基因型分布为GG：186例（38.9%），AG：222例（46.4%），AA：70例（14.6%）；PNPLA3基因rs738409等位基因的分布为CC：269例（56.3%），CG：177例（37.0%），GG：32例（6.7%）。总体而言，FDTF1多态性与脂肪变性或纤维化程度无关。然而，在无脂肪变性的患者中，AA基因型与晚期纤维化相关[AA：8/20（40.0%），AG：6/70（8.5%），GG：9/57（16.1%），P = 0.003]。相比之下，PNPLA3的次要等位基因与脂肪变性和晚期纤维化均相关（P < 0.001）。两种单核苷酸多态性均不影响治疗反应。
FDFT1中的次要等位基因与非脂肪变性亚组而非脂肪变性亚组中的晚期纤维化相关。这可能反映了CHC脂肪变性和非脂肪变性患者在纤维化进展中的不同代谢途径。
