Effect of Genetic Variation on Salt, Sweet, Fat and Bitter Taste by Andre Dias A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Nutritional Sciences University of Toronto © Copyright by Andre Dias 2014 Effect of Genetic Variation on Salt, Sweet, Fat and Bitter Taste Andre Dias Doctor of Philosophy Department of Nutritional Sciences University of Toronto 2014 Abstract Background: Taste is one of the primary determinants of food intake and taste function can be influenced by a number of factors including genetics. However, little is known about the relationship between genetic variation, taste function, food preference and intake. Objective: To examine the effect of variation in genes involved in the perception of salt, sweet, fat and bitter compounds on taste function, food preference and consumption. Methods: Subjects were drawn from the Toronto Nutrigenomics and Health Study, a population of healthy men (n=487) and women (n = 1058). Dietary intake was assessed using a 196-item food frequency questionnaire (FFQ) and food preference was assessed using a 63-item food preference checklist. Subsets of individuals were phenotyped to assess taste function in response to salt (n=95), sucrose (n=95), oleic acid (n=21) and naringin (n=685) stimuli. Subjects were genotyped for Single Nucleotide Polymorphisms (SNPs) in candidate genes. Results: Of the SNPs examined in putative salt taste receptor genes (SCNN1(A, B, D, G), TRPV1), the rs9939129 and rs239345 SNPs in the SCNN1B gene and rs8065080 in the TRPV1 gene were associated with salt taste. In the TAS1R2 gene, the rs12033832 was associated with sucrose taste and sugar intake. The rs1077242 SNP in the bitter taste receptor gene TAS2R19 was ii associated with naringin taste and both grapefruit intake and preference. In the putative fat taste receptor CD36 the rs1761667 and rs1984112 SNPs were associated with intake of total, polyunsaturated and monounsaturated fats as well as oleic acid taste. Conclusions: Our findings demonstrate that genetic variation is associated with differences in taste function, food preference and intake across a number of taste modalities. iii Acknowledgments It has been more than a decade since I first arrived at the Department of Nutritional Sciences. Still in high school, I was amazed by the work that was being carried out, the dedication of the staff and students to their discipline, and the people who seemed larger than life. I am still amazed. The department has been my home for the last 10 years. It is where I have had some of my most joyous, and most humbling, experiences. To the hundreds of people who have built it, and created this place of learning, thank you. This thesis would not have happened without the patience and guidance of my supervisor, Dr. Ahmed El-Sohemy. Ahmed, I first heard you speak long before I contemplated grad school. At the time I was advised to, if at all possible, be more like you. It was sound advice ;) Learning with you during these last 4.5 years has been an incredible experience. Your passion, belief in your principles, and strategic approach in all situations is inspiring. Additionally, your mentorship style is quite simply phenomenal. Your willingness to give your students as much help as necessary, while granting them the freedom and independence to chart their own course, is commendable. Few professors get this right and, in my life, this has made all the difference. In our time together you have allowed me to accomplish so much, both in and outside the lab. I will forever be in your debt for this. Thank you for a truly incredible experience. From grade 11 till the end of my undergraduate studies I had 3 parents; my mom, my dad and Dr. Vladimir Vuksan. Dr. Vuksan, my days working with you at the Risk Factor Modification Center are by far some of my fondest. Aside from my parents, no one has had a greater impact on my development than you. You taught me to think on my feet, pushed me beyond my limits, and gave me the learning experience of a lifetime. I cannot thank you enough. Looking back, you were part of almost all my major life decisions over the last decade. You introduced me to research, were one of the primary reasons I decided to join U of T, pushed me to pursue graduate school, and have supported me as a mentor and friend ever since. Thank you. I look forward to staying in touch over the next decade and many more afterwards. Moira and Winnie, thank you for your hard work and friendship. Without your help, and the help of your students, I don’t think my PhD work would have been possible. Working with you both at George Brown College was probably the most fun I have ever had and I will always fondly iv remember my time there. Chef Ian, thanks for putting up with all of the inane restrictions of my work and for keeping me well fed at all times. I can’t tell you how jealous the other graduate students were when they found how well I dined. Candace, Lara, Catherine, Pia, Geremy, and Cecilia, thank you so much for all of your hard work and the numerous 5AM mornings you endured with me. I couldn’t have done it without you. Mom and Dad, no one could ask for better parents than Nandita and I. As I get older I am able to more fully appreciate the immense effort you took to provide us with the best opportunities and push us to our full potential. From teaching me math and driving me to an array of activities, to giving me the confidence to start my own business, you have been integral in building all of the skills I have today. Thank you. Nandita, thank you for being the best big sister in the world. You have been helping me through school and expanding my horizons for as long as I can remember. Without you, I definitely wouldn’t have got here. Fidel, thanks for being such an awesome and supportive brother in law. You have been there for me since the day I met you. Rohit, we shared most of this journey together and I very grateful I got to do it with you. Thanks for being an awesome roommate, friend, and cousin. Komal, you are by far the best girlfriend anyone could ask for. I can't count the number of times you opted to study with me in the library, rather than have a night out. You were beside me the entire way, pushing me when I was unmotivated, calming me when I was frazzled and cheering me up whenever I was down. I couldn’t have done it without you. Thank you for being so incredible and so supportive. To my lab mates, thank you for your help, feedback, and friendship. Daiva, you’re my homegirl! Thank you for always being there for me in a pinch. Bibiana, thanks for your help and friendship. Joanne and Laura, I miss you. You made my first two years as a grad student truly amazing; the lab hasn’t been the same since you left. To all of the people who made my time at U of T so enjoyable, thank you. Dennis, we have supervised each other, been colleagues, and, run a company together. You are one of my closest friends and definitely played a huge role in getting me here today, thank you. Jovana, you are both incredibly capable and down to earth, a rare combination. Thanks for being a great colleague and an even better friend. Elsa, you are one of the most caring and kind hearted people v I have ever come across. Thank you for your friendship and please continue to inspire the rest of us to change the world. Julie and Shannon, you opened my eyes to world I never knew existed. Thanks for your friendship and organizing LTS Sandy Lake. Chuck, you were personality of our department. No one did more to make everyone feel welcome. Conrad, Dave, Sonali, and Jake, thank you for your training and support. Without you, I would never have had the opportunity to transition to a new career. Lastly, I would like to thank He Song. You are one of the kindest, most helpful people I know. I could never have finished this thesis without your guidance and help. Thank you. vi Table of Contents Abstract…....................................................................................................................................... ii Acknowledgments.......................................................................................................................... iv Table of Contents.......................................................................................................................... vii List of Tables ................................................................................................................................. xi List of Figures............................................................................................................................... xii List of Abbreviations ................................................................................................................... xiii Chapter 1 Introduction..................................................................................................................1 Chapter 2 Literature Review ........................................................................................................3 2.1 General taste.........................................................................................................................3 2.2 Taste physiology ..................................................................................................................4 2.3 Taste and food intake...........................................................................................................6 2.4 Salt taste...............................................................................................................................7