The Impact of Genetic Variations in ADORA2A in the Association between Caffeine Consumption and Sleep

• Published in: Genes Vol. 10; no. 12; p. 1021
• Main Authors: Erblang, Mégane, Drogou, Catherine, Gomez-Merino, Danielle, Metlaine, Arnaud, Boland, Anne, Deleuze, Jean François, Thomas, Claire, Sauvet, Fabien, Chennaoui, Mounir
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06-12-2019; MDPI
• Subjects: Adenosine; Adolescent; Adult; Alleles; Anxiety; Caffeine; Caffeine - administration & dosage; Coffee; Consumers; Consumption; Female; Food and Nutrition; Gene polymorphism; Genetic diversity; Genetics; Genotype & phenotype; Haplotypes; Homeostasis; Human genetics; Human health and pathology; Humans; Insomnia; Life Sciences; Linkage analysis; Linkage Disequilibrium; Male; Middle Aged; Pharmacodynamics; Polymorphism; Polymorphism, Single Nucleotide; Populations and Evolution; Questionnaires; Receptor, Adenosine A2A - genetics; Single-nucleotide polymorphism; Sleep - genetics; Sleep and wakefulness; Sleep deprivation; Sleep disorders; Sleep Initiation and Maintenance Disorders - genetics; Tissues and Organs; sleep; caffeine; ADORA2A; adenosine A2A receptor; polymorphisms; Sleep; Polymorphisms; Adenosine A2A receptor; Caffeine
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes10121021

ADORA2A has been shown to be responsible for the wakefulness-promoting effect of caffeine and the 1976T>C genotype (SNP rs5751876, formerly 1083T>C) to contribute to individual sensitivity to caffeine effects on sleep. We investigate the association between six single nucleotide polymorphisms (SNP) from ADORA2A and self-reported sleep characteristics and caffeine consumption in 1023 active workers of European ancestry aged 18-60 years. Three groups of caffeine consumers were delineated: low (0-50 mg/day, less than one expresso per day), moderate (51-300 mg/day), and high (>300 mg/day). We found that at caffeine levels higher than 300 mg/day, total sleep time (TST) decreased (
= 13.9,
< 0.01), with an increase of insomnia (ORa [95%CI] = 1.5 [1.1-1.9]) and sleep complaints (ORa [95%CI] = 1.9 [1.1-3.3]), whatever the ADORA2A polymorphism. Odds ratios were adjusted (ORa) for sex, age, and tobacco. However, in low caffeine consumers, lower TST was observed in the T allele compared to homozygote rs5751876 and rs3761422 C carriers. Conversely, higher TST was observed in rs2298383 T allele compared to C and in rs4822492G allele compared to the homozygote C (
< 0.05). These 4 SNPs are in strong linkage disequilibrium. Haplotype analysis confirmed the influence of multiple ADORA2a SNPs on TST. In addition, the rs2298383 T and rs4822492 G alleles were associated with higher risk of sleep complaints (Ora = 1.9 [1.2-3.1] and Ora = 1.5 [1.1-2.1]) and insomnia (Ora = 1.5 [1.3-2.5] and Ora = 1.9 [1.3-3.2). The rs5751876 T allele was associated with a decreased risk of sleep complaints (Ora = 0.7 [0.3-0.9]) and insomnia (Ora = 0.5 [0.3-0.9]). Our results identified ADORA2A polymorphism influences in the less-than-300-mg-per-day caffeine consumers. This opens perspectives on the diagnosis and pharmacology of sleep complaints and caffeine chronic consumption.