ABO Genotype, “Blood-Type” Diet and Cardiometabolic Risk Factors
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ABO Genotype, “Blood-Type” Diet and Cardiometabolic Risk Factors by Jingzhou Wang A thesis submitted in conformity with the requirements for the degree of Master of Science (M.Sc.) Graduate Department of Nutritional Sciences University of Toronto © Copyright by Jingzhou Wang 2014 ABO Genotype, “Blood-Type” Diet and Cardiometabolic Risk Factors Jingzhou Wang Master of Science Graduate Department of Nutritional Sciences University of Toronto 2014 Abstract The ‘Blood-Type’ diet advises individuals to eat according to their ABO blood group to optimize health without the support of science evidence. The objective of this study was to determine whether consumption of a diet in accordance with an individual’s ABO genotype is associated with various biomarkers of cardiometabolic health. Study subjects (n=1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four blood type diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. The results show that adherence to the Type-A, Type-AB, and Type-O diets were associated with favourable profile of certain cardiometabolic risk factors (P<0.05); however, these dietary effects were not dependent on someone’s ABO blood group. Therefore, the findings do not support the “Blood-Type” diet hypothesis. ii Acknowledgments I would not have reached this stage without the help of others. Here, I want to express my sincere gratitude to the people who made my life in the department truly enjoyable. First of all, I want to thank my supervisor, Dr. Ahmed El-Sohemy for his excellent support throughout my Master’s training. His passion in the field of nutrigenomics attracts me to pursue this graduate degree and his brilliant ideas allow me to work on an interesting project. With his approachability and patience, I was able to learn and improve my thinking, writing, speaking skills significantly. His generosity and flexibility has also enabled me to discover career opportunities and to develop my soft skills in other settings. It was truly my honour to be a student for Ahmed. I am very grateful for all the opportunities and knowledge he has offered. I cannot imagine a better mentor. Second, I would like to thank Dr. Richard Bazinet and Dr. Elena Comelli for offering wonderful support as my committee members. Their critical feedback and constructive advice have helped me to further develop my critical thinking and to mature as a graduate student. It was also a privilege to have two of my most admiring undergraduate professors to serve on my advisory committee. I have also benefited tremendously from the teaching of Dr. Paul Corey and Dr. Tony Hanley. Their high levels of expertise in statistics and epidemiology have helped me build a solid foundation in my research project. I also want to specifically thank Dr. Harvey Anderson, who has played a significant role in my undergraduate training. Without his guidance, I would not fall in love with research. His consistent support, even after I leave the lab, has been invaluable. Third, I want to thank all the past and present members in the El-Sohemy team. The thesis would not be completed in a timely manner without the effort of all past students. I am also very iii grateful to receive the support from Bibiana Garcia-Bailo, Daiva Nielsen, Ouxi Tian, Andre Dias, Nanci Guest and Joseph Jamnik in both academic and social circumferences. The quality of my research project improved significantly thanks to their input. It was a pleasure to be a part of the big family. Fourth, I would like to thank all the staff members and students in the department. Louisa Kung and Emeliana D'Souza were always there to give an extra hand. Clara Cho and Diana Sanchez-Hernandez were my first mentors in the research field and have taught me a significant amount of knowledge and skills that are useful in my future career. I am also equally grateful for the experiences and encouragement offered by my colleagues and teammates in the departmental student union and volleyball team. The assistances of all these fellows have no doubt facilitated the completion of my research project. I also gratefully acknowledge the funding sources that made this thesis possible: the Ontario Graduate Scholarship program and the Advanced Foods and Materials Network. In addition, I was fortunate to be able to attend an international conference thanks to the generous support from Dr. Ahmed El-Sohemy and School of Graduate Studies at University of Toronto. My last gratitude goes to my family. My parents have offered invaluable guidance in my entire life. Without the support of my father, Song Wang, I would not have had the opportunity to study aboard. I want to specifically thank for my mother, Yu Liu, who passed away from liver cancer when I was 15 years old. Watching Animal Planet with my mother made me fall in love with biology when I was young; losing my closest person due to cancer led me to pursue a career in life sciences. To her I dedicate this thesis. Thank you all! iv “In a group of three people, there is always something I can learn from. Choose to follow the strengths of others, use the shortcomings to reflect upon ourselves." Confucious, 500 BC v Table of Contents TABLE OF CONTENTS VI LIST OF TABLES IX LIST OF FIGURES X LIST OF APPENDIX XI Chapter 1: Introduction and Literature Review 1.1 INTRODUCTION 1 1.2 “BLOOD-TYPE” DIET 1 1.3 ABO BLOOD GROUP 2 1.3.1 ABO SYSTEM 2 1.3.2 ABO BLOOD GROUP AND DISEASES 3 1.3.3 BLOOD GROUPS AND NUTRITION 4 1.4 CARDIOMETABOLIC DISEASES 6 1.4.1 PREVALENCE AND ETIOLOGY 6 1.4.2 BIOMARKERS OF RISK 6 1.4.3 RISK FACTORS 9 1.5 SUMMARY AND RATIONALE 10 1.6 HYPOTHESIS AND ORGANIZATION OF THESIS 11 Chapter 2: Effect of ABO Genotype on Cardiometabolic Risk Factors 2.1 ABSTRACT 12 2.2 INTRODUCTION 13 2.3 METHODS 14 vi 2.3.1 STUDY DESIGN AND PARTICIPANTS 14 2.3.2 ABO GENOTYP IDENTIFICATION 14 2.3.3 CARDIOMETABOLIC RISK FACTOR ASSESSMENT 15 2.3.4 STATISTICAL ANALYSIS 16 2.4 RESULTS 16 2.5 DISCUSSION 22 Chapter 3: Effect of "Blood-Type" Diet on Cardiometablic Risk Factors 3.1 ABSTRACT 23 3.2 INTRODUCTION 24 3.3 MATERIAL AND METHODS 27 3.3.1 STUDY DESIGN AND PARTICIPANTS 27 3.3.2 DIETARY ADHERENCE SCORE ASSESSMENT 27 3.3.3 CARDIOMETABOLIC RISK FACTOR ASSESSMENT 28 3.3.4 STATISTICAL ANALYSIS 28 3.4 RESULTS 29 3.5 DISCUSSION 38 Chapter 4: Effect of matching ABO genotype to "Blood-Type" Diet on Cardiometabolic Risk Factors 4.1 ABSTRACT 41 4.2 INTRODUCTION 42 4.3 MATERIAL AND METHODS 42 4.3.1 STUDY DESIGN AND PARTICIPANTS 42 4.3.2 ABO GENOTYPE IDENTIFICATION 43 vii 4.3.3 DIETARY ADHERENCE SCORE ASSESSMENT 43 4.3.4 CARDIOMETABOLIC RISK FACTOR ASSESSMENT 43 4.3.5 STATISTICAL ANALYSIS 43 4.4 RESULTS 44 4.5 DISCUSSION 54 Chapter 5: Overview and General Discussion 5.1 OVERVIEW 56 5.2 LIMITATIONS 58 5.3 FUTURE DIRECTIONS 60 5.4 IMPLICATION 61 REFERENCE 62 APPENDIX 70 viii List of Tables TABLE 2-1: SUBJECT CHARACTERISTICS BY ABO GENOTYPE 19 TABLE 3-1A: THE "TYPE-A " DIET CHARACTERISTICS 34 TABLE 3-1B: CARDIOMETABOLIC RISK FACTORS BY TERTILES OF “TYPE-A” DIET SCORE 34 TABLE 3-2A: THE "TYPE-AB" DIET CHARACTERISTICS 35 TABLE 3-2B: CARDIOMETABOLIC RISK FACTORS BY TERTILES OF “TYPE-AB” DIET SCORES 35 TABLE 3-3A: THE "TYPE-B" DIET CHARACTERISTICS 36 TABLE 3-3B: CARDIOMETABOLIC RISK FACTORS BY TERTILES OF "TYPE-B" DIET SCORES 36 TABLE 3-4A: THE "TYPE-O" DIET CHARACTERISTICS 37 TABLE 3-4B: CARDIOMETABOLIC RISK FACTORS BY TERTILES OF "TYPE-O" DIET SCORES 37 TABLE 4A: CARDIOMETABOLIC RISK FACTORS BY "TYPE-A" DIET SCORES AND ABO GENOTYPE 47 TABLE 4B: CARDIOMETABOLIC RISK FACTORS BY "TYPE-AB" DIET SCORES AND ABO GENOTYPE 50 TABLE 4C: CARDIOMETABOLIC RISK FACTORS BY "TYPE-B" DIET SCORES AND ABO GENOTYPE 52 TABLE 4D: CARDIOMETABOLIC RISK FACTORS BY "TYPE-O" DIET SCORES AND ABO GENOTYPE 53 ix List of Figures FIGURE 2-1: ABO BLOOD TYPE ASSESSMENT BY GENOTYPING SINGLE NUCLEOTIDE POLYMORPHISMS 15 FIGURE 2-2: ABO BLOOD GROUP DISTRIBUTION IN THE ENTIRE TNH COHORT (A) AND BY ETHNOCULTURAL GROUPS (B) 17 FIGURE 2-3: LEVELS OF FASTING GLUCOSE IN INDIVIDUALS WITH DIFFERENT ABO BLOOD GROUPS 20 FIGURE 2-4: LEVELS OF FASTING INSULIN IN INDIVIDUALS WITH DIFFERENT ABO BLOOD GROUPS 21 FIGURE 3-1: TOTAL NUMBER OF RECOMMENDED ITEMS TO EAT (A) OR AVOID (B) IN FOUR MAJOR FOOD GROUPS LISTEDIN THE FFQ FOR EACH "BLOOD-TYPE" DIET 30 FIGURE 3-2: DIET SCORE DISTRIBUTION FOR EACH "BLOOD TYPE” DIET 31 FIGURE 4-1: NUMBER OF INDIVIDUALS WITH MATCHED AND UNMATCHED BLOOD GROUPS ACROSS THE TERTILE TERTILE OF EACH “BLOOD-TYPE” DIET SCORE 45 FIGURE 4-2: THE ASSOCIATION BETWEEN TERTILES OF “TYPE-A” DIET SCORES AND FASTING INSULIN IN SUBJECTS WITH BLOOD TYPE A AND THE OTHERS 48 FIGURE 4-3: THE ASSOCIATION BETWEEN TERTILES OF “TYPE-A” DIET SCORES AND FASTING GLUCOSE IN SUBJECTS WITH BLOOD TYPE A AND THE OTHERS 49 FIGURE 4-4: THE ASSOCIATION BETWEEN TERTILES OF “TYPE-AB” DIET SCORES AND FASTING GLUCOSE IN SUBJECTS WITH BLOOD TYPE A AND THE OTHERS 51 x List of Appendix TABLE: FOOD ITEMS INCLUDED IN THE "BLOOD-TYPE" DIET SCORE CALCULATION 65 xi Chapter 1: Introduction and Literature Review 1.1 Introduction The “Blood-Type” diet is a set of nutritional guidelines that advocate people to eat according to their blood group.