AMPK subunits harbor largely non-overlapping genetic determinants for body fat mass, glucose- and cholesterol metabolism

内分泌学 内科学 单核苷酸多态性 胰岛素 胆固醇 生物 碳水化合物代谢 安普克 糖尿病 医学 遗传学 基因型 基因 蛋白激酶A 生物化学
作者
Elko Randrianarisoa,Angela Lehn-Stefan,Johannes Krier,Anja Böhm,Martin Heni,Martin Hrabě de Angelis,Andreas Fritsche,Hans‐Ulrich Häring,Norbert Stefan,Harald Staiger
出处
期刊:The Journal of Clinical Endocrinology and Metabolism [Oxford University Press]
被引量:2
标识
DOI:10.1210/jcem/dgz020
摘要

Abstract Context AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all seven subunit genes on adiposity, glucose- and lipid metabolism has not been systematically studied yet. Objective To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, total-, LDL- and HDL-cholesterol and triglycerides. Study Design and Methods A cohort of 2789 non-diabetic subjects from the Tübingen Family study of type-2 diabetes, metabolically characterized by oral glucose tolerance test and genotyped by genome-wide SNP array was analyzed. Results We identified largely non-overlapping SNP sets across four AMPK genes (PRKAA1, PRKAA2, PRKAG2, PRKAG3) associated with adiposity, insulin sensitivity, insulin secretion, blood glucose, total-/LDL-cholesterol or HDL-cholesterol, respectively. A genetic score of body-fat-increasing alleles revealed per-allele effect sizes on BMI of +0.22 kg/m² (p=2.3·10-7), insulin sensitivity of -0.12·1019 L²/mol² (p=9.9·10-6) and 2-h blood glucose of +0.02 mmol/L (p=0.0048). Similar effects on blood glucose were observed with scores of insulin-sensitivity-reducing, insulin-secretion-reducing and glucose-raising alleles, respectively. A genetic cholesterol score increased total- and LDL-cholesterol by 1.17 mg/dL per allele (p=0.0002 and p=3.2·10-5, respectively), and a genetic HDL score decreased HDL-cholesterol by 0.32 mg/dL per allele (p=9.1·10-6). Conclusions We describe largely non-overlapping genetic determinants in AMPK genes for diabetes-/atherosclerosis-related traits which reflect the metabolic pathways controlled by the enzyme. Formation of trait-specific genetic scores revealed additivity of allele effects, with body-fat-raising alleles reaching a marked effect size.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
踏实万天发布了新的文献求助10
1秒前
星辰大海应助lll采纳,获得10
1秒前
网球发布了新的文献求助10
1秒前
1秒前
Harish完成签到,获得积分10
1秒前
2秒前
马铃薯发布了新的文献求助10
2秒前
乐乐应助紫定能行采纳,获得10
3秒前
独特妙竹完成签到 ,获得积分20
3秒前
3秒前
香蕉觅云应助kiuikiu采纳,获得10
4秒前
KK完成签到,获得积分20
4秒前
5秒前
黄晓完成签到,获得积分10
5秒前
Tina完成签到 ,获得积分10
5秒前
123456发布了新的文献求助10
5秒前
共享精神应助典雅的俊驰采纳,获得10
5秒前
6秒前
华健发布了新的文献求助10
6秒前
6秒前
Goodluck完成签到,获得积分10
7秒前
KK发布了新的文献求助10
8秒前
大气的一德完成签到,获得积分20
10秒前
wawaeryu发布了新的文献求助50
10秒前
10秒前
10秒前
充电宝应助Chen二月三石采纳,获得10
10秒前
abcdefg完成签到,获得积分10
11秒前
小白完成签到,获得积分20
11秒前
feiying88发布了新的文献求助10
12秒前
zcvxd完成签到,获得积分10
13秒前
13秒前
枫影发布了新的文献求助10
14秒前
14秒前
14秒前
斯文败类应助QiangWang1991采纳,获得10
14秒前
庞扬发布了新的文献求助20
14秒前
小白发布了新的文献求助30
14秒前
Ava应助WTX采纳,获得10
15秒前
15秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3974882
求助须知:如何正确求助?哪些是违规求助? 3519431
关于积分的说明 11198315
捐赠科研通 3255698
什么是DOI,文献DOI怎么找? 1797904
邀请新用户注册赠送积分活动 877237
科研通“疑难数据库(出版商)”最低求助积分说明 806219