AMY1基因拷贝数与葡萄糖吸收及内脏脂肪体积相关，但与胰岛素抵抗无关。

AMY1 Gene Copy Number Correlates With Glucose Absorption and Visceral Fat Volume, but Not with Insulin Resistance.

作者信息

Barber Thomas M, Bhatti Ahsan A, Elder Patrick J D, Ball Sarah P, Calvez Ronan, Ramsden David B, Cuthbertson Dan J, Pfeiffer Andreas F, Burnett David, Weickert Martin O

机构信息

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Coventry, UK.

出版信息

J Clin Endocrinol Metab. 2020 Oct 1;105(10). doi: 10.1210/clinem/dgaa473.

DOI:10.1210/clinem/dgaa473

PMID:32697825

Abstract

BACKGROUND

The human amylase gene (AMY1) has a broad copy number (CN) variation that may associate with body mass index.

METHODS

Deoxyribonucleic acid was extracted from urine (n = 74) and serum (n = 6) samples (Protein, Fiber and Metabolic Syndrome [ProFiMet] cohort), and buccal (n = 17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital polymerase chain reaction. The association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analyzed with Pearson's correlation coefficient (CC). For the healthy, euglycemic OSC cohort, glycemic response to OSC was analyzed with independent sample t-tests (subgroups: high AMY1 CN 9-12, n = 10; low AMY1 CN 4-6, n = 7).

RESULTS

There were significant inverse correlations of AMY1 CN with total visceral fat volume (CC -0.33; P = 0.004) and positive correlations of AMY1 CN with oral glucose insulin sensitivity score (derived from an oral glucose tolerance test, CC 0.26; P = 0.02), serum HDL-cholesterol (CC 0.325; P = 0.003), and serum adiponectin (CC 0.249; P = 0.026). Linear regression multivariate analysis (adiponectin as dependent variable), showed independent association of adiponectin with AMY1 CN (Beta = 0.29; P = 0.03). There were no significant associations between AMY1 CN and clamp-derived M-value, homeostasis model assessment of insulin resistance (IR), hepatic endogenous glucose production, fecal floral signature, or macronutrient dietary preference. Delta (mean) change in blood glucose concentration (fasting to 30-minutes post-OSC) was significantly greater in the high versus low AMY1 CN subgroups (mean 1.7 mmol/l [SEM 0.6] vs 0.9 mmol/l [SEM 0.9], respectively; P = 0.016).

CONCLUSIONS

High AMY1 CN associates with a favorable metabolic profile (lower visceral fat volume, higher serum adiponectin, enhanced glucose absorption following oral glucose, and OSC), but not with whole-body or hepatic IR.

摘要

背景

人类淀粉酶基因（AMY1）具有广泛的拷贝数（CN）变异，可能与体重指数相关。

方法

从尿液（n = 74）和血清（n = 6）样本（蛋白质、纤维与代谢综合征[ProFiMet]队列）以及颊部（n = 17）样本（口服淀粉激发试验[OSC]队列）中提取脱氧核糖核酸，并通过液滴数字聚合酶链反应评估AMY1 CN。用Pearson相关系数（CC）分析ProFiMet队列中AMY1 CN与代谢状态综合标志物的关联。对于健康、血糖正常的OSC队列，用独立样本t检验分析对OSC的血糖反应（亚组：高AMY1 CN 9 - 12，n = 10；低AMY1 CN 4 - 6，n = 7）。

结果

AMY1 CN与总内脏脂肪体积呈显著负相关（CC -0.33；P = 0.004），与口服葡萄糖胰岛素敏感性评分呈正相关（源自口服葡萄糖耐量试验，CC 0.26；P = 0.02）、与血清高密度脂蛋白胆固醇呈正相关（CC 0.325；P = 0.003）以及与血清脂联素呈正相关（CC 0.249；P = 0.026）。线性回归多变量分析（以脂联素为因变量）显示脂联素与AMY1 CN存在独立关联（β = 0.29；P = 0.03）。AMY1 CN与钳夹衍生的M值、胰岛素抵抗（IR）的稳态模型评估、肝脏内源性葡萄糖生成、粪便菌群特征或常量营养素饮食偏好之间无显著关联。高AMY1 CN亚组与低AMY1 CN亚组相比，血糖浓度的Δ（平均）变化（空腹至OSC后30分钟）显著更大（分别为平均1.7 mmol/l[标准误0.6]和0.9 mmol/l[标准误0.9]；P = 0.016）。