Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.
BACKGROUND
Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis.


METHODS
To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking.


RESULTS
The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol.


CONCLUSIONS
These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.
Iwamoto
N
N
Division of Metabolism and Endocrinology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849, Japan. iwamotsu@nature.email.ne.jp
Ogawa
Y
Y
Kajihara
S
S
Hisatomi
A
A
Yasutake
T
T
Yoshimura
T
T
Mizuta
T
T
Hara
T
T
Ozaki
I
I
Yamamoto
K
K
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D003062:Codon; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003062:Codon; D018343:Receptors, Adrenergic, beta-2