학술논문

A Pilot Genome‐Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH
Document Type
article
Author
Gawrieh, SamerGuo, XiuqingTan, JingyiLauzon, MarieTaylor, Kent DLoomba, RohitCummings, Oscar WPillai, SreekumarBhatnagar, PallavKowdley, Kris VYates, KatherineWilson, Laura AChen, Yii‐Der IdaRotter, Jerome IChalasani, NagaAllende, DanielaDasarathy, SrinivasanMcCullough, Arthur JPenumatsa, RevathiDasarathy, JaividhyaLavine, Joel EAbdelmalek, Manal FBashir, MustafaBuie, StephanieDiehl, Anna MaeGuy, CynthiaKigongo, ChristopherKopping, MarikoMalik, DavidPiercy, DawnRagozzino, LindaSandrasegaran, KumarVuppalanchi, RajBrunt, Elizabeth MCattoor, TheresaCarpenter, DanielleFreebersyser, JanetKing, DebraLai, JinpingNeuschwander, Brent ASiegner, JoanStewart, SusanTorretta, SusanWriston, KristinaGonzalez, Maria CardonaDavila, JodieJhaveri, MananMukhtar, NizarNess, ErikPoitevin, MichelleQuist, BrookSoo, SherilynnAng, BrandonBehling, CynthiaBhatt, ArchanaMiddleton, Michael SSirlin, ClaudeAkhter, Maheen FBass, Nathan MBrandman, DanielleGill, RyanHameed, BilalMaher, JacquelineTerrault, NorahUngermann, AshleyYeh, MatthewBoyett, SherryContos, Melissa JKirwin, SherriLuketic, Velimir ACPuri, PuneetSanyal, Arun JSchlosser, JoleneSiddiqui, Mohammad SYost‐Schomer, LeslieFowler, KathrynKleiner, David EDoo, Edward CHall, SherryHoofnagle, Jay HRobuck, Patricia RSherker, Averell HTorrance, RebeccaBelt, PatriciaClark, Jeanne MDodge, JohnDonithan, MicheleIsaacson, MilanaLazo, MarianaMeinert, JillMiriel, LauraSmith, JacquelineSmith, MichaelSternberg, AliceTonascia, JamesNatta, Mark LWagoner, AnnetteYamada, Goro
Source
Hepatology Communications. 3(12)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Liver Disease
Digestive Diseases
Clinical Trials and Supportive Activities
Human Genome
Hepatitis
Clinical Research
Genetics
Chronic Liver Disease and Cirrhosis
2.1 Biological and endogenous factors
Aetiology
Oral and gastrointestinal
NASH Clinical Research Network
Clinical sciences
Language
Abstract
A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P