Caffeine Consumption and Interaction with ADORA2A, CYP1A2 and NOS1 Variants Do Not Influence Age at Onset of Machado-Joseph Disease.

BACKGROUND: The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3, is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease. METHODS: a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 (ADORA2A), rs2298383 (ADORA2A), rs762551 (CYP1A2) and rs478597 (NOS1) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats (p < 0.05). RESULTS: 171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516). DISCUSSION: Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A, CYP1A2 and NOS1.

The effect of caffeine on exercise performance is not influenced by ADORA2A genotypes, alone or pooled with CYP1A2 genotypes, in adolescent athletes.

PURPOSE: This study investigated the influence of the different genotypes of ADORA2A (1976 C > T, rs 5751876), alone or pooled with CYP1A2 (163 C > A rs 762551) genotypes, on the ergogenic effects of caffeine (CAF) on various aspects of physical performance in male adolescent athletes. METHODS: Ninety male adolescent athletes (age = 15.5 ± 2 years) were classified according to their genotypes for 1976 C > T ADORA2A (TT homozygous or CADORA2A allele carriers) and 163 C > A CYP1A2 (AA homozygous or CCYP1A2 allele carriers). Participants were further divided in four groups (1-TTADORA2A + AACYP1A2; 2-TTADORA2A + AC/CCCYP1A2; 3-AACYP1A2 + CT/CCADORA2A;4-AC/CCCYP1A2 + CT/CCADORA2A). Using a randomized, crossover, counterbalanced, and double-blind design, participants ingested CAF (6 mg kg-1) or a placebo (PLA, 300 mg of cellulose) one hour before performing a sequence of physical tests: handgrip strength, agility test, countermovement jump (CMJ), Spike Jump (SJ), sit-ups, push-ups, and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). RESULTS: CAF enhanced handgrip strength (CAF: 35.0 ± 9.2 kg force; PLA: 33.5 ± 8.9 kg force; p = 0.050), CMJ height (CAF: 49.6 ± 12.3 cm; PLA: 48.3 ± 13.6 cm; p = 0.013), SJ height (CAF: 54.7 ± 13.3 cm; PLA: 53.1 ± 14.8 cm; p = 0.013), number of sit-ups (CAF: 37 ± 8; PLA: 35 ± 8; p = 0.001), and distance covered on the Yoyo IR1 test (CAF: 991.6 ± 371.0 m; PLA: 896.0 ± 311.0 m; p = 0.001), This CAF-induced improvement on exercise performance was, however, independent of genotypes groups (all p > 0.05). CAF had no effect on agility (CAF: 15.8 ± 1.2 s; PLA: 15.9 ± 1.3 s; p = 0.070) and push-up (CAF: 26.6 ± 12.0; PLA: 25.0 ± 11.0; p = 0.280) tests. CONCLUSION: The acute caffeine intake of 6.0 mg.kg-1 improves several aspects of physical performance, which seems to be independent of ADORA2A genotypes, alone or in combination with CYP1A2 genotypes.

Can the Brazilian Caffeine Expectancy Questionnaires Differentiate the CYP1A2 and ADORA2A Gene Polymorphisms?-An Exploratory Study with Brazilian Athletes.

This study investigated the ability of the Brazilian Caffeine Expectancy Questionnaire (CaffEQ-BR), full and brief versions, to differentiate genetic profiles regarding the polymorphisms of the CYP1A2 (rs 762551) and ADORA2A (rs 5751876) genes in a cohort of Brazilian athletes. One-hundred and fifty participants were genotyped for CYP1A2 and ADORA2A. After the recruitment and selection phase, 71 (90% male and 10% female, regular caffeine consumers) completed the CaffEQ-BR questionnaires and a self-report online questionnaire concerning sociodemographic data, general health status, and frequency of caffeine consumption. The order of completion of the CaffEQ-BR questionnaires was counterbalanced. The concordance between the full and brief versions of the CaffEQ-BR was analyzed using the intraclass correlation coefficient (ICC). To determine the discriminatory capacity of the questionnaires for genotype, the receiver operating characteristic (ROC) curve was applied for sensitivity and specificity (significance level of 5%). Mean caffeine intake was 244 ± 161 mg·day−1. The frequency of AA genotypes for CYP1A2 was 47.9% (n = 34) and 52.1% (n = 37) for C-allele carriers (AC and CC). The frequencies of TT genotypes for ADORA2A were 22.7% (n = 15) and 77.3% (n = 51) for C-allele carriers (TC and CC). All CaffEQ-BR factors, for the full and brief versions, were ICCs > 0.75, except for factor 6 (anxiety/negative effects; ICC = 0.60), and presented ROC curve values from 0.464 to 0.624 and 0.443 to 0.575 for CYP1A2 and ADORA2A. Overall, the CaffEQ-BR (full and brief versions) did not show discriminatory capacity for CYP1A2 and ADORA2A gene polymorphisms. In conclusion, the CaffEQ-BR was not able to differentiate genotypes for the CYP1A2 or ADORA2A genes in this group of Brazilian athletes.

Caffeine and Exercise Performance: Possible Directions for Definitive Findings.

Caffeine is one of the most studied supplements in the world. Studies correlate its use to increased exercise performance in endurance activities, as well as its possible ergogenic effects for both intermittent and strength activities. Recent findings show that caffeine may increase or decrease exercise performance. These antagonist responses may occur even when using the same dosage and for individuals with the same characteristics, making it challenging to explain caffeine's impact and applicability. This review article provides an analytic look at studies involving the use of caffeine for human physical performance, and addresses factors that could influence the ergogenic effects of caffeine on different proposed activities. These factors subdivide into caffeine effects, daily habits, physiological factors, and genetic factors. Each variable has been focused on by discussions to research related to caffeine. A better understanding and control of these variables should be considered in future research into personalized nutritional strategies.

Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients?

AIM: Levodopa is first line treatment of Parkinson's disease (PD). However, its use is associated with the presence of motor fluctuations and dyskinesias. In recent years, adenosine A2A receptor (A2AR) is rising as a therapeutic target for PD. The aim of the present study was to investigate whether ADORA2A is associated with levodopa adverse effects. PATIENTS & METHODS: Two hundred and eight PD patients on levodopa therapy were investigated. rs2298383 and rs3761422 at the ADORA2A gene were genotyped by allelic discrimination assays. RESULTS: A trend for association was observed for both polymorphism and diplotypes with dyskinesia. CONCLUSION: The present results should be considered as positive preliminary evidence. Further studies are needed to determine the association between ADORA2A and dyskinesia. Original submitted 3 December 2014; Revision submitted 13 February 2015.