谷氨酰胺27谷氨酸β2-肾上腺素能受体变体与高甘油三酯血症及脂肪肝的发生有关。

Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.

作者信息

Iwamoto N, Ogawa Y, Kajihara S, Hisatomi A, Yasutake T, Yoshimura T, Mizuta T, Hara T, Ozaki I, Yamamoto K

机构信息

Division of Metabolism and Endocrinology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849, Japan.

出版信息

Clin Chim Acta. 2001 Dec;314(1-2):85-91. doi: 10.1016/s0009-8981(01)00633-7.

DOI:10.1016/s0009-8981(01)00633-7

PMID:11718682

Abstract

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.

摘要

背景

非酒精性脂肪性肝炎（NASH）与脂质、葡萄糖和能量代谢相关。β-肾上腺素能受体在能量消耗调节中发挥重要作用，部分是通过刺激脂肪分解来促进脂质动员。

方法

为评估16和27密码子处的β2-肾上腺素能受体（B2AR）基因多态性在脂肪肝发生中是否常见，我们调查了251名无血缘关系、未使用药物且无大量饮酒迹象的健康日本男性。

结果

肥胖受试者（BMI>25.0 kg/m²，n = 151）和非肥胖受试者（BMI≤25.0 kg/m²，n = 100）之间，16和27密码子处B2AR基因突变的等位基因频率无差异。Gly16纯合子的高密度脂蛋白胆固醇（HDL-C）水平低于Arg16纯合子（1.50±0.4对1.32±0.3 mmol/l，p = 0.014）。然而，Gly16等位基因频率与脂肪肝无显著关联。Gln27Glu27杂合子的血清甘油三酯（TG）浓度高于Gln27Gln27纯合子（1.62±0.93对2.21±1.67 mmol/l，p = 0.013）。无论体重分类如何，在所有受试者中均观察到这种相关性。单因素分析表明，携带杂合Gln27Glu突变等位基因的受试者脂肪肝患病率显著高于未突变者（Glu27等位基因频率，0.07对0.12，p = 0.047；比值比，1.92；95%置信区间，1.01 - 3.68）。然而，多因素逻辑回归模型显示，脂肪肝患病率与稳态模型评估（HOMA）指数、BMI、甘油三酯和HDL-胆固醇显著相关。