咖啡摄入量与肥胖、代谢综合征和 2 型糖尿病风险的关系：一项孟德尔随机研究。

Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes: a Mendelian randomization study.

机构信息

Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

出版信息

Int J Epidemiol. 2015 Apr;44(2):551-65. doi: 10.1093/ije/dyv083. Epub 2015 May 22.

DOI:10.1093/ije/dyv083

PMID:26002927

Abstract

BACKGROUND

Coffee is one of the most widely consumed beverages. We tested the hypothesis that genetically high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof.

METHODS

We included 93,179 individuals from two large general population cohorts in a Mendelian randomization study. We tested first whether high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof, in observational analyses; second, whether five genetic variants near the CYP1A1, CYP1A2 and AHR genes are associated with coffee intake; and third, whether the genetic variants are associated with obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Finally, we tested the genetic association with type 2 diabetes in a meta-analysis including up to 78,021 additional individuals from the DIAGRAM consortium.

RESULTS

Observationally, high coffee intake was associated with low risk of obesity, metabolic syndrome and type 2 diabetes. Further, high coffee intake was associated with high body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides and total cholesterol and with low high-density lipoprotein cholesterol, but not with glucose levels. In genetic analyses, 9-10 vs 0-3 coffee-intake alleles were associated with 29% higher coffee intake. However, genetically derived high coffee intake was not associated convincingly with obesity, metabolic syndrome, type 2 diabetes, body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol or glucose levels. Per-allele meta-analysed odds ratios for type 2 diabetes were 1.01 (0.98-1.04) for AHR rs4410790, 0.98 (0.95-1.01) for AHR rs6968865, 1.01 (0.99-1.03) for CYP1A1/2 rs2470893, 1.01 (0.98-1.03) for CYP1A1/2 rs2472297 and 0.98 (0.95-1.01) for CYP1A1 rs2472299.

CONCLUSIONS

High coffee intake was associated observationally with low risk of obesity, metabolic syndrome and type 2 diabetes, and was associated observationally with related components thereof, but with no genetic evidence to support corresponding causal relationships.

摘要

背景

咖啡是最广泛饮用的饮料之一。我们检验了一个假设，即高咖啡摄入量与肥胖、代谢综合征和 2 型糖尿病风险降低相关，也与这些疾病的相关成分降低相关。

方法

我们在一项孟德尔随机化研究中纳入了来自两个大型一般人群队列的 93179 名个体。我们首先在观察性分析中检验高咖啡摄入量是否与肥胖、代谢综合征和 2 型糖尿病风险降低相关，以及与这些疾病的相关成分降低相关；其次，检验位于 CYP1A1、CYP1A2 和 AHR 基因附近的 5 个遗传变异是否与咖啡摄入量相关；最后，检验这些遗传变异是否与肥胖、代谢综合征和 2 型糖尿病相关，以及与这些疾病的相关成分降低相关。最后，我们在包括来自 DIAGRAM 联盟的多达 78021 名额外个体的荟萃分析中检验了与 2 型糖尿病的遗传关联。

结果

观察性分析显示，高咖啡摄入量与肥胖、代谢综合征和 2 型糖尿病风险降低相关。此外，高咖啡摄入量与体重指数、腰围、体重、身高、收缩压/舒张压、甘油三酯和总胆固醇升高以及高密度脂蛋白胆固醇降低相关，但与血糖水平无关。在遗传分析中，9-10 个 vs 0-3 个咖啡摄入量等位基因与咖啡摄入量增加 29%相关。然而，遗传上高的咖啡摄入量与肥胖、代谢综合征、2 型糖尿病、体重指数、腰围、体重、身高、收缩压/舒张压、甘油三酯、总胆固醇、高密度脂蛋白胆固醇或血糖水平没有明显的关联。2 型糖尿病的每等位基因荟萃分析的比值比为 AHR rs4410790 的 1.01（0.98-1.04）、AHR rs6968865 的 0.98（0.95-1.01）、CYP1A1/2 rs2470893 的 1.01（0.99-1.03）、CYP1A1/2 rs2472297 的 1.01（0.98-1.03）和 CYP1A1 rs2472299 的 0.98（0.95-1.01）。