1. COFFEE CONSUMPTION: A GENETIC APPROACH Roseane Santos, BS, MS, PhD Associate Professor, South University School of Pharmacy Email: rsantos@southuniversity.edu 3 rd International Conference on Clinical Pharmacy Atlanta, Georgia, December 7-9 2015

2. Objectives O Some background on the evolution of coffee studies O Creation of a consortium to study with a genomic approach coffee and its effects O Coffee Consumption and development of diabetes type 2 as an example O Conclusions 2

3. Introduction O Coffee is in fact a very complex mixture that varies according with the origin of the beans and roasting processes. O Caffeine, polycyclic phenols such as chlorogenic acids are some of the most studied constituents from coffee O Various properties are attributed to those compounds. O Some effects are opposite and leads to controversial conclusions. O A new approach is to look into possible effects of drugs through genetic and genomic studies. 3

4. The Coffee and Caffeine Genetics Consortium O Composed by researchers from all over the globe. O Purpose is to identify DNA loci associated with habitual coffee consumption. O The technique utilized is called genome-wide meta- analysis (GWMA). O Some loci already known as the one that codes for CYP 1A2 (caffeine metabolism) were confirmed O New ones are being identified, opening new targets to understand the effects of coffee on human health 4

5. Coffee Consumption and Obesity: an example O Chlorogenic acids (CGA’s), Caffeine and Coffee restored the Na + /K + ATPase and AChE-ase activity in Diabetic rats; O There is a decrease in Na+/ K+ ATPase activity and an increase in AChE ase in Diabetic neuropathy O Mol Cell Biochem (2014) 388: 277-286 O Rio Grande do Sul, Brazil 5

6. Endothelial dysfunction/ Insulin resistance O Longevity genes, Silent information regulator 2 (Sir-2) and Sirtuin (Sirt-1) are highly expressed in endotelial dysfunction (ED); O p66 Shc redox enzyme is linked to apoptosis, induces oxidative stress, vascular senescence O Sirt-1 regulates the expression of p66Shc O New target to address in Diabetes type 2 O Aging and Endothelial dysfunction/ Insulin Resistance, JAHA (2013) doi 10.1161 O Padova, Italy 6

7. Adipokines : new target in diabetes O Adiponectin decrease is associated with obesity, major receptors Adipo R1 (muscle), R2 (liver) O Coffee consumption increases adiponectin levels O Adiponectin is secreted by adipocytes and belongs to a group named adipokines O Gene is located at Chr.3q27 with known SNPs O Cardiovascular Diabetology 2014, 13: 103 O Telaviv, Israel 7

8. Coffee and Inflammation O Coffee intake mitigated inflammation and obesity- induced insulin resistance in the skeletal muscle of high-fat diet induced obese mice O Genes associated with insulin response in the muscle O Another target for investigation O Genes Nutr 2014, 9: 389 O Tokyo, Japan 8

9. Genetic/Genomic studies O Decaffeinated green coffee attenuates diet- induced obesity and Insulin resistance in mice O Coffee downregulate genes involved in adipogenesis and inflammation in visceral adipose tisue O Another target for investigation O Evidence-Based Complementary and Alternative Medicine 2014, ID 718379 O Seoul, Korea 9

10. Conclusion O Genetic and genomic studies comparing populations that drink coffee regularly with non- coffee drinkers are leading to new findings in terms of genes that are involved in the physiopathology of important diseases, such as diabetes, O Those genes (proteins) are new targets for the treatment of diseases and at same time are helping to elucidate the intricate network of effects of coffee and its multitude of bioactive components on human health. 10

11. Acknlowledgements In Memorian Dr. DARCY ROBERTO ANDRADE LIMA

12. Questions?? 12