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RESEARCH PRODUCT

TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C

Fabio Salvatore MacalusoAntonio CraxìDi Marco VitoDaniela CabibiStefania GrimaudoRosaria Maria PipitoneSalvatore PettaSandro SferrazzaCalogero CammàMarcello Maida

subject

0301 basic medicineLiver CirrhosisMalesteatosiIL28BStatistics as TopicGastroenterologySeverity of Illness IndexCohort Studies0302 clinical medicineFibrosisNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseMembrane ProteinFatty liverHepatitis CMiddle AgedItalyLiver030211 gastroenterology & hepatologyFemaleHumanAdultmedicine.medical_specialtyLiver Cirrhosisteatosis; CHC; IL28B; PNPLA3; TM6SF2; Adult; Cohort Studies; Female; Hepatitis C Chronic; Humans; Interleukins; Italy; Lipase; Liver; Male; Membrane Proteins; Middle Aged; Severity of Illness Index; Statistics as Topic; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; HepatologyTM6SF203 medical and health sciencesInternal medicineSeverity of illnessmedicineHumansPNPLA3Hepatologybusiness.industryInterleukinsMembrane ProteinsOdds ratioLipaseHepatologyHepatitis C ChronicInterleukinmedicine.diseaseFatty LiverCHC030104 developmental biologyEndocrinologyInterferonsSteatosisCohort Studiebusiness

description

Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosis severity (P = 0.63), compared to noncarriers. Prevalence and severity of steatosis were reduced in IL28B C allele carriers (P = 0.005) and elevated in PNPLA3 G allele carriers (P < 0.001). After adjustment for age, gender, body mass index and homoeostasis model assessment score, steatosis severity was independently associated with IL28B rs12979860 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55–0.86, P = 0.001) and PNPLA3 rs738409 (OR 1.84, 95% CI 1.46–2.83, P < 0.001), but not TM6SF2 rs58542926 (OR 1.48, 95% CI 0.82–2.69, P = 0.19). Variants of TM6SF2 (30.9% vs. 25%, P = 0.40), IL28B and PNPLA3 were not directly associated with fibrosis severity, although variants of IL28B and PNPLA3 promoted steatosis (OR 1.36, 95% CI 1.06–1.75, P = 0.01) that in turn is associated with severe fibrosis. Conclusions In G1 CHC patients, TM6SF2 rs58542926 does not affect the histological severity of liver damage. However, IL28B rs12979860 and PNPLA3 rs738409 modify steatosis.

yearjournalcountryeditionlanguage
2016-01-01
10.1111/liv.12918http://hdl.handle.net/10447/228587