Specifically PNPLA3-mediated accumulation of liver fat in obese patients with type 2 diabetes.
BACKGROUND
Recently, it has been shown in the general population that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC), independently of visceral adiposity and insulin resistance.


OBJECTIVE
In this study, we set out to determine whether LFC, evaluated using (1)H-MR spectroscopy, was associated with PNPLA3 rs738409 polymorphism in people with type 2 diabetes. We also evaluated the influence of this polymorphism on the relationship between LFC and either visceral adiposity or carotid intima media thickness (CIMT).


METHODS
A total of 218 type 2 diabetic patients were included in this study.


METHODS
LFC, area of visceral fat, and CIMT were measured.


RESULTS
A total of 139 (63.7%) patients had steatosis. The rs738409 minor G allele was associated with LFC. The number of patients with steatosis was significantly higher among minor G allele carriers in comparison to C allele homozygote carriers (70.3 vs. 57.2%; P=0.04) In the subgroup of C allele homozygote carriers, LFC correlated with body mass index (r=0.27; P=0.003) and visceral fat area (r=0.30; P=0.002), but not with CIMT. In the subgroup of minor G allele carriers, LFC correlated inversely with CIMT (r=-0.23; P=0.03), but not with body mass index or with visceral fat area. In multivariate logistic regression, the relationship between the highest quartile of CIMT and steatosis was different according to adiponutrin polymorphism.


CONCLUSIONS
This study confirms that in people with type 2 diabetes, LFC is related to rs738409 polymorphism. The lack of a relationship with visceral obesity and the inverse correlation with CIMT suggest that fatty liver associated with the minor G allele of the PNPLA3 rs738409 polymorphism may not be linked to metabolic disorders.
Petit
Jean-Michel
JM
Université de Bourgogne, Centre de Recherche Institute National de la Santé, Dijon cedex, France. jean-michel.petit@chu-dijon.fr
Guiu
Boris
B
Masson
David
D
Duvillard
Laurence
L
Jooste
Valerie
V
Buffier
Perrine
P
Terriat
Beatrice
B
Bouillet
Benjamin
B
Brindisi
Marie-Claude
MC
Loffroy
Romaric
R
Robin
Isabelle
I
Hillon
Patrick
P
Cercueil
Jean-Pierre
JP
Verges
Bruno
B
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015992:Body Mass Index; D002339:Carotid Arteries / Q000473:pathology*; D002353:Carrier State; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D048909:Diabetes Complications / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D017539:Tunica Intima / Q000473:pathology*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002784:Cholesterol; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent