The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine

<p>Abstract</p> <p>Background</p> <p>Although caffeine supplementation improves performance, the ergogenic effect is variable. The cause(s) of this variability are unknown. A (C/A) single nucleotide polymorphism at intron 1 of the cytochrome P450 (CYP1A2) gene influences caffeine metabolism and clinical outcomes from caffeine ingestion. The purpose of this study was to determine if this polymorphism influences the ergogenic effect of caffeine supplementation.</p> <p>Methods</p> <p>Thirty-five trained male cyclists (age = 25.0 ± 7.3 yrs, height = 178.2 ± 8.8 cm, weight = 74.3 ± 8.8 kg, VO₂max = 59.35 ± 9.72 ml·kg^-1·min^-1) participated in two computer-simulated 40-kilometer time trials on a cycle ergometer. Each test was performed one hour following ingestion of 6 mg·kg^-1of anhydrous caffeine or a placebo administered in double-blind fashion. DNA was obtained from whole blood samples and genotyped using restriction fragment length polymorphism-polymerase chain reaction. Participants were classified as AA homozygotes (N = 16) or C allele carriers (N = 19). The effects of treatment (caffeine, placebo) and the treatment × genotype interaction were assessed using Repeated Measures Analysis of Variance.</p> <p>Results</p> <p>Caffeine supplementation reduced 40 kilometer time by a greater (<it>p </it>< 0.05) magnitude in AA homozygotes (4.9%; caffeine = 72.4 ± 4.2 min, placebo = 76.1 ± 5.8 min) as compared to C allele carriers (1.8%; caffeine = 70.9 ± 4.3 min, placebo = 72.2 ± 4.2 min).</p> <p>Conclusions</p> <p>Results suggest that individuals homozygous for the A allele of this polymorphism may have a larger ergogenic effect following caffeine ingestion.</p

Endocrine Disruptor Regulation of MicroRNA Expression in Breast Carcinoma Cells

Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer