PMID- 22961556
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20141120
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 57
IP  - 2
DP  - 2013 Feb
TI  - Solute carrier family 2 member 1 is involved in the development of nonalcoholic 
      fatty liver disease.
PG  - 505-14
LID - 10.1002/hep.26052 [doi]
AB  - Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic 
      bases, but the associated variants are uncertain. The aim of the present study 
      was to identify genetic variants that could help to prognose and further 
      understand the genetics and development of NAFLD. Allele frequencies of 3,072 
      single-nucleotide polymorphisms (SNPs) in 92 genes were characterized in 69 NAFLD 
      patients and 217 healthy individuals. The markers that showed significant 
      allele-frequency differences in the pilot groups were subsequently studied in 451 
      NAFLD patients and 304 healthy controls. Besides this, 4,414 type 2 diabetes 
      mellitus (T2DM) cases and 4,567 controls were genotyped. Liver expression of the 
      associated gene was measured and the effect of its potential role was studied by 
      silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and 
      the consequences of oleic acid (OA)-enriched medium on lipid accumulation in 
      siSLC2A1-THLE2 cells were studied by gene-expression analysis, dihydroethidium 
      staining, BODIPY, and quantification of intracellular triglyceride content, 
      respectively. Several SNPs of SLC2A1 (solute carrier family 2 [facilitated 
      glucose transporter] member 1) showed association with NAFLD, but not with T2DM, 
      being the haplotype containing the minor allele of SLC2A1 sequence related to the 
      susceptibility to develop NAFLD. Gene-expression analysis demonstrated a 
      significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional 
      analyses of transcriptome profiles drove us to demonstrate that in vitro 
      silencing of SLC2A1 induces an increased OS activity and a higher lipid 
      accumulation under OA treatment. CONCLUSIONS: Genetic variants of SLC2A1 are 
      associated with NAFLD, and in vitro down-regulation of this gene promotes lipid 
      accumulation. Moreover, the oxidative response detected in siSLC2A1-THLE2 cells 
      corroborated the antioxidant properties previously related to this gene and 
      linked the most representative clinical characteristics of NAFLD patients: 
      oxidative injury and increased lipid storage.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Vazquez-Chantada, Mercedes
AU  - Vazquez-Chantada M
AD  - CIC bioGUNE, Centro de Investigacion Biomedica en red de Enfermedades Hepaticas y 
      Digestivas (CIBERehd), Derio, Spain.
FAU - Gonzalez-Lahera, Aintzane
AU  - Gonzalez-Lahera A
FAU - Martinez-Arranz, Ibon
AU  - Martinez-Arranz I
FAU - Garcia-Monzon, Carmelo
AU  - Garcia-Monzon C
FAU - Regueiro, Manuela M
AU  - Regueiro MM
FAU - Garcia-Rodriguez, Juan L
AU  - Garcia-Rodriguez JL
FAU - Schlangen, Karin A
AU  - Schlangen KA
FAU - Mendibil, Inaki
AU  - Mendibil I
FAU - Rodriguez-Ezpeleta, Naiara
AU  - Rodriguez-Ezpeleta N
FAU - Lozano, Juan J
AU  - Lozano JJ
FAU - Banasik, Karina
AU  - Banasik K
FAU - Justesen, Johanne M
AU  - Justesen JM
FAU - Joergensen, Torben
AU  - Joergensen T
FAU - Witte, Daniel R
AU  - Witte DR
FAU - Lauritzen, Torsten
AU  - Lauritzen T
FAU - Hansen, Torben
AU  - Hansen T
FAU - Pedersen, Oluf
AU  - Pedersen O
FAU - Veyrie, Nicolas
AU  - Veyrie N
FAU - Clement, Karine
AU  - Clement K
FAU - Tordjman, Joan
AU  - Tordjman J
FAU - Tran, Albert
AU  - Tran A
FAU - Le Marchand-Brustel, Yannik
AU  - Le Marchand-Brustel Y
FAU - Buque, Xabier
AU  - Buque X
FAU - Aspichueta, Patricia
AU  - Aspichueta P
FAU - Echevarria-Uraga, Jose J
AU  - Echevarria-Uraga JJ
FAU - Martin-Duce, Antonio
AU  - Martin-Duce A
FAU - Caballeria, Joan
AU  - Caballeria J
FAU - Gual, Philippe
AU  - Gual P
FAU - Castro, Azucena
AU  - Castro A
FAU - Mato, Jose M
AU  - Mato JM
FAU - Martinez-Chantar, Maria L
AU  - Martinez-Chantar ML
FAU - Aransay, Ana M
AU  - Aransay AM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20121127
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (SLC2A1 protein, human)
RN  - 2UMI9U37CP (Oleic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Diabetes Mellitus, Type 2/genetics
MH  - Fatty Liver/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Gene Silencing
MH  - Genetic Predisposition to Disease
MH  - Glucose Transporter Type 1/biosynthesis/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Non-alcoholic Fatty Liver Disease
MH  - Oleic Acid/pharmacology
MH  - Oxidative Stress/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Transcriptome
EDAT- 2012/09/11 06:00
MHDA- 2013/04/05 06:00
CRDT- 2012/09/11 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/08/06 00:00 [accepted]
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
AID - 10.1002/hep.26052 [doi]
PST - ppublish
SO  - Hepatology. 2013 Feb;57(2):505-14. doi: 10.1002/hep.26052. Epub 2012 Nov 27.