Gln27Glu β2-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 less than or equal to 25.0 kg/m(2), n = 100). The Gly 16 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. (C) 2001 Elsevier Science B.V. All rights reserved.