Topic Highlight
Copyright ©The Author(s) 2016.
World J Hepatol. Jul 18, 2016; 8(20): 827-837
Published online Jul 18, 2016. doi: 10.4254/wjh.v8.i20.827
Table 1 List of genome/exome wide association studies and loci identified for non-alcoholic fatty liver disease
Ref.Phenotype associated withAncestry of samples includedGenotyping platformDiscovery sample sizeReplication sample sizeGenes
Romeo et al[6], 2008Increased hepatic fat levels and inflammationHispanic, African American and European American individualsPerlegen Sciences Custom array (12138 NS variation)2111 individuals with MRS measured hepatic steatosisNonePNPLA3
Chalasani et al[15], 2010Features of hepatic histologyNon-Hispanic white womenIllumina (324,623 SNPs)236, non-Hispanic white womenNoneFDFT1, rs343062 (Chr 7), COL13A1, rs6591182 (Chr 11), EFCAB4B, rs2499604 (chr 1), PZP, rs1421201 (Chr 18) rs2710833 (Chr 4)
Speliotes et al[16], 2011CT measured hepatic steatosisEuropean american including AmishAffymetrix, Illumina7126 with CT measured hepatic steatosis592/1405PNPLA3, NCAN, PPP1R3B, GCKR, LYPLAL1
Kawaguchi et al[3], 2012NAFLDJapaneseIllumina529 patients consisting of four NAFLD subgroups (Matteoni’s classification)NonePNPLA3, SAMM50, PARVB, HS3ST1-HSP90AB2P, YIPF1
Kitamoto et al[66], 2013NAFLDJapaneseIllumina392 NAFLD and 934 controls172 NAFLD and 1012 controlsPNPLA3, SAMM50, PARVB gene
Kozlitina et al[19], 2014MRS measured hepatic steatosisHispanic, African, American and EuropeanIllumina2,736NonePNPLA3 and TM6SF2
Table 2 Functional role of major genes associated with non-alcoholic fatty liver disease identified by genome/exome wide association studies
GeneProteinCellular location1Function1Chromosome location2No. of exons and size2Pathway/biologic function1Tissues expressed1
PNPLA3Patatin-like phospholipase domain-containing protein 3Lipid dropletsTriacyl glycerol lipase and acylglycerol O-cyltransferase activitiesChromosome 22: 43,923,739-43,964,488 (forward strand)9 (2805 bp)Triacyl glycerol degradation and in glycerol-lipid metabolismLiver, gall bladder, kidney, exocrine pancreas, seminal vesicles, intestine and salivary glands
TM6SF2Transmembrane 6 superfamily member 2ER and the ER-golgi intermediate compartmentRegulation of fat in liver influencing triglyceride secretion and lipid droplet contentChromosome 19: 19,264,364-19,273,391 (reverse strand)10 (1505 bp)Promotes very low density lipoprotein exportLiver and intestine
SAMM50Sorting and assembly machinery component 50 homologOuter mitochondrial membraneAssembly of beta-barrel proteinsChromosome 22: 43,955,421-44,010,531 (forward strand)15 (1717)Transport to the Golgi and subsequent modification and mitochondrial protein importLiver, muscle, skeletal, lung adipocyte, colon and other tissues
PARVBParvin, betaCytoplasmInvolved in the reorganization of the actin cytoskeleton and formation of lamellipodiaChromosome 22: 44,024,277-44,172,949 (forward strand)13 (5429 bp)ERK signaling and focal adhesionLiver, muscle, skeletal, lung adipocyte, colon and other tissues
NCANNeurocanExtracellular, Golgi lumenModulates neuronal adhesion and neurite growth during developmentChromosome 19: 19,211,973-19,252,233 (forward strand)15 (6387 bp)DevelopmentalLiver, muscle, skeletal, lung adipocyte, colon and other tissues
PPP1R3BProtein phosphatase 1, regulatory subunit 3BGlycogen granuleActs as glycogen targeting subunit for phosphatase PP1Chromosome 8: 9,136,255-9,151,574 (reverse strand)2 (5548 bp)Regulating glycogen synthesisLiver, skeletal muscle
GCKRGCKRCytoplasm, nucleusInhibits glucokinase by forming an inactive complex with this enzyme. The affinity of GCKR for GK is modulated by fructose metabolitesChromosome 2: 27,496,842-27,523,684 (forward strand)19 (2186 bp)Carbohydrate metabolismLiver, pancreas, colon and other tissues
LYPLAL1Lysophospholipase-like 1CytoplasmDepalmitoylating activityChromosome 1: 219,173,844-219,212,865 (forward strand)5 (1898 bp)Negative regulation of golgi to plasma membrane protein transportLiver, muscle, skeletal, lung adipocyte, colon and other tissues