Dataset Information

Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia.

ABSTRACT: The liver enzyme cytochrome P450 1A2 (CYP1A2) is responsible for 90% of caffeine metabolism, while caffeine exerts many of its effects via antagonist binding to adenosine A2a receptors (ADORA2A). This study aimed to examine whether functional single nucleotide polymorphisms (SNPs) in 1976T?>?C (ADORA2A; rs5751876) and -163C?>?A (CYP1A2; rs762551) influence the effect of caffeine on the postprandial glucose (GLU) response to a carbohydrate meal. We report that individuals with the 1976T?>?C CC, but not CT/TT genotypes display elevated GLU levels after consuming caffeine and carbohydrate (CHO?+?CAFF) versus carbohydrate only (CHO). The GLU area under the curve (AUC) was also greater during the CHO?+?CAFF condition compared to the CHO condition in CC, but not the CT/TT genotypes. The -163C?>?A AC/CC, but not AA, genotypes displayed greater GLU concentrations 60-min post meal during CHO?+?CAFF versus CHO. Our data suggest that caffeine-induced impairments in postprandial glycaemia are related to 1976T?>?C and -163C?>?A SNPs.

SUBMITTER: Banks NF

PROVIDER: S-EPMC6642114 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia.

Banks N F NF Tomko P M PM Colquhoun R J RJ Muddle T W D TWD Emerson S R SR Jenkins N D M NDM

Scientific reports 20190719 1

The liver enzyme cytochrome P450 1A2 (CYP1A2) is responsible for 90% of caffeine metabolism, while caffeine exerts many of its effects via antagonist binding to adenosine A2a receptors (ADORA2A). This study aimed to examine whether functional single nucleotide polymorphisms (SNPs) in 1976T > C (ADORA2A; rs5751876) and -163C > A (CYP1A2; rs762551) influence the effect of caffeine on the postprandial glucose (GLU) response to a carbohydrate meal. We report that individuals with the 1976T > C CC, b ...[more]

PMID: 31324842

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Project description:Aims/hypothesisImbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.MethodsWe dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.ResultsIn individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states.Conclusions/interpretationThese results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Project description:Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (-163C > A, rs762551; characterized such as "fast" (AA genotype) and "slow" caffeine metabolizers (C-carriers)) and ADORA2A (1976T > C; rs5751876; characterized by "high" (TT genotype) or "low" sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d-1) ingested 3 mg·kg-1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the -163C > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8-4.3%, p = 0.001-0.022, effect size = 0.17-0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg-1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.

Dataset Information

Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia.

Publications

Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia.

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