Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts.
OBJECTIVE
We investigated whether polymorphisms in candidate genes involved in lipid metabolism and type 2 diabetes are related to liver fat content.


METHODS
Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS) in 302 Finns, in whom single nucleotide polymorphisms (SNPs) in acyl-CoA synthetase long-chain family member 4 (ACSL4), adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2), and the three peroxisome proliferator-activated receptors (PPARA, PPARD, and PPARG) were analyzed. To validate our findings, SNPs significantly associated with liver fat content were studied in two independent cohorts and related to surrogate markers of liver fat content.


RESULTS
In the Finnish subjects, polymorphisms in ACSL4 (rs7887981), ADIPOR2 (rs767870), and PPARG (rs3856806) were significantly associated with liver fat content measured with (1)H-MRS after adjusting for age, gender, and BMI. Anthropometric and circulating parameters were comparable between genotypes. In the first validation cohort of approximately 600 Swedish men, ACSL4 rs7887981 was related to fasting insulin and triglyceride concentrations, and ADIPOR2 rs767870 to serum gamma glutamyltransferase concentrations after adjusting for BMI. The SNP in PPARG (rs3856806) was not significantly associated with any relevant metabolic parameter in this cohort. In the second validation cohort of approximately 3000 subjects from Western Finland, ADIPOR2 rs767870, but not ACSL4 rs7887981 was related to fasting triglyceride concentrations.


CONCLUSIONS
Genetic variation, particularly in the ADIPOR2 gene, contributes to variation in hepatic fat accumulation in humans.
Kotronen
Anna
A
Division of Diabetes, Department of Medicine, University of Helsinki, FIN-00029 Helsinki, Finland.
Yki-Järvinen
Hannele
H
Aminoff
Anna
A
Bergholm
Robert
R
Pietiläinen
Kirsi H
KH
Westerbacka
Jukka
J
Talmud
Philippa J
PJ
Humphries
Steve E
SE
Hamsten
Anders
A
Isomaa
Bo
B
Groop
Leif
L
Orho-Melander
Marju
M
Ehrenborg
Ewa
E
Fisher
Rachel M
RM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D005234:Fatty Liver / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
C475420:ADIPOR2 protein, human; D005819:Genetic Markers; D054419:Receptors, Adiponectin; D014280:Triglycerides