Gene - Diet Interaction and Weight Loss: A Focus on Asians

By Anh Nguyen-Hoang, RNT, DCN, CNHC, FBANT, Abdul-Rahman Toufik, Wireko Andrew Awuah, Heather Tillewein, Jessica Honig, Yves Miel H. Zuniga, FRSPH, AFCHSM, CHM, CPH, Sailee Bhambere, BDS, MPH, Duha Shella, Alice Colescu, Candice Carpenter, MD, MBA, MPH, EdM

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Nguyen-Hoang A, Toufik A, Awuah W, Tillewein, Honig J, Zuniga Y, Bhambere, Shella D, Colescu A, Carpenter C. Diet-interaction and weight loss: A focus on asians. HPHR. 2022;63. 10.54111/0001/KKK6

Gene - Diet Interaction and Weight Loss: A Focus on Asians

Abstract

Obesity is a global public health issue because adult obesity is a gateway to other chronic diseases such as diabetes, cardiovascular diseases. The European Committee has recently recognized obesity as a chronic condition. The Asian population has often been ignored in research although they account for about 60% of the global population. The development of obesity in Asians is multifactorial and somewhat different from White counterparts. Our current review demonstrated that diet strategies play an essential role in the treatment and prevention for obesity, although accumulative evidence demonstrates that genetic influences should be taken into consideration with these strategies.

Introduction

The Worth Health Organization (WHO) defines body mass index (BMI) as “a person’s weight in kilograms divided by the square of the person’s height in meters (kg/m2).” BMI has been well recognized as an effective measurement to identify overweight individuals and subsequent health risks for those individuals. Nguyen-Hoang (2019) emphasised that the increasing level of individuals with overweight to extremely obese BMIS is thought to accompany the increasing risk of health problems in these individuals.1 Obesity is characterized by abnormal or excessive fat accumulation that may impair health. The obesity epidemic can create obesity-related conditions that can lead to preventable, premature death. These conditions include: heart disease, stroke, type 2 diabetes, and various types of cancers. 2 The 2017 Global Burden of Disease (GBD) estimates that at least 4 million people die annually as a result of obesity or being overweight4. WHO further noted that worldwide obesity has nearly tripled since 1975, affecting both adults and children.

Accumulative evidence on non-communicable diseases demonstrated that Asian adults get more body fat and have greater risks of diabetes and cardiovascular diseases at their lower BMI in comparison with non-Asian populations. In particular, Asians have 3 to 5 per cent more total body fat than white Europeans with the same BMI. In Asia, there has been a dramatic increase in cases of obesity across the years. 3 Based on GBD data, Asia –particularly South Asia–recorded the highest obesity-related deaths and disability-adjusted life years (DALYs) from 1990 to 2017 (158.3% [95% UI 77.3%, 403.9%] for deaths and 165.9% [95% UI 83.3%, 400.7%] for DALYs).4 South Asians also have higher levels of body fat and are more likely to develop abdominal obesity, which could explain their elevated risk of type 2 diabetes and cardiovascular disease. 5-6 The expert panel of WHO consultation developed Asian regional BMI cut-off points 7 to minimize these risks. In this suggested category, a body mass index of 23 kg/m2 and more is considered overweight.

Diet and genotype interactions on weight loss in Asians

Genes influencing eating behaviors and weight concerns exist, unique to persons of Asian descent. However, the research remains nascent. Such research is needed to create effective nutritional and health care protocols across the life span. 8-11 A  twenty-year study9 demonstrated that Asian adult women have more than double the risk of diabetes onset at markedly lower body weight, such that for every 11lbs gained – the risk of Type-2 Diabetes elevated by 84%. Possible evolutionary and body-type specific traits, including famine-prevention fat-storing nuances, central obesity trends, genetically vulnerable determinants,  and cravings for carbohydrate and/or high-fat foods in elevated frequency, may play a role.9-10 Health care delivery examined in the United States and the United Kingdom lacked protocols for clinical discussion of weight-related issues such as diabetes or food-specific cravings 8-9,12-13. Similarly, factors in Asian immigrants may further instigate genetic predisposition to problematic eating behaviors such as emotional eating or high carbohydrate cravings due to immigration stressors, racism, and adoption of a Westernized diet. Globally, Asian specific eating behaviors and barriers to healthy weight remain under-explored. Unique to Asian risk factors regarding healthy weight, a 2021 longitudinal, qualitative study from the United Kingdom noted that low physical activity in Asian immigrants was correlated with acculturation and Western diets high in saturated fat (e.g. pizza, pastries, French fries). This lead to a greater understanding of the driving forces, of  education or nutritional counselling to mitigate these adverse factors.8 Furthermore, additional research into Asian genetics (separated by regionalism) may help further specify the unique educational and nutritional recommendations necessary to speak to a variety of Asians, both as a collective entity, and individualized sub-ethnicities.12-13

 

Cumulative evidence suggests that the genetic profile plays a significant role in the development of obesity as well as different responses to a weight management intervention. To date, about 400 genes are associated with obesity and these genes are responsible for up to 70% of inter-individual variations in BMI. As mentioned in the earlier section, Asians commonly have lower BMI than Whites, but in the same obesity classes, they have a higher proportion of body fat than Whites have. Notably, each BMI unit increase could put Asians at higher risk for hypertension and type 2 diabetes, compared with non-Asians.

 

To our best knowledge, genome-wide association (GWAS) studies have identified over 750 loci associated with obesity.15 These loci vary by ethnicity, although the majority of GWAS results were conducted in individuals of European ancestry. Among genes, the obesity-associated gene (FTO) variants have been mostly well-acknowledged with obesity-related traits. In the European population, individuals with FTO rs9939609 variant are more likely to gain weight and increase the risk for the development of obesity compared with non-risk allele carriers. Moreover, GWAS studies repeated in multiple ethnicities including Asians confirms the effect size is consistent, but differences in the allelic frequency across ethnic groups (e.g. ~60% in Europeans – 17% in Asians). Variants in the FTO genes including rs9939609, rs8050136, and rs11076023 have the potential to elevate the risk of obesity and type 2 diabetes in Asians. A meta-analysis on Indians demonstrated that each of the rs9939609 risk allele could contribute to a 0.3 kg/m2 increase in BMI16. Individuals carrying the rs11076023 Allele T, regardless of the highest fiber intake, had a higher waist circumference than those with AA genotype17. Similarly, among individuals consuming high carbohydrates (more than 70% of energy), the rs8050136 Allele A carriers increased nearly 3 times the risk of obesity compared to individuals carrying the homozygous one (CC). A study in the Mongolian population also demonstrated that rs8050136 CA/AA genotypes were associated with a significantly increased risk of type 2 diabetes, as compared with the CC genotype, while adjusting for age, sex and BMI18.

 

In terms of waist circumference, the GWAS study in the Japanese population (N= 173,430 people ) found that 112 new gene/ loci in the Japanese population shed light on the influence of PRDM6-CEP120 on the BMI and waist circumference on this population. It has never been reported in Europeans, suggesting that it may be exclusive to the Asian population.19 A meta-analysis of  GWASs on the East-Asian population showed three new loci near the CEP120, TSC22D2, and SLC22A2 genes to be associated with waist circumference20.

 

Taste perceptions or taste preferences are also associated with dietary choices, which may influence healthy or unhealthy food intake.21 Genetic studies have partly shed light on how genetic information can help to target individuals’ taste buds. 6-n-propylthiouracil (PROP) taster is one of the most studied taste phenotypes. PROP taster are classified into three groups including PROP supertasters, medium taster and non-tasters, who perceive PROP as most bitter, moderately bitter, and tasteless, respectively. A recent study found that Asians are more likely to be PROP supertasters, thermal tasters, and low sweet likers compared to Caucasians22. In this study, Asian research participants are Chinese, Indians, Pakistan, and other Asian backgrounds, but it did not provide specific information about participants who identified as Caucasian. There also was a larger taste response to salty, sour, and metallic tastes (p<0.05) in Asians rather than Caucasians. The research on genes related to taste preferences has yielded promising results for personalised nutrition, but its application to clinical practice and the prevention and treatment of obesity is still in the embryonic stage.

 

There are genetic links to obesity in a specific cohort of Asians which reveal dopamine processes and its capacity to transform food into energy. Evidence has emerged on the gene DRD2 – a dopamine receptor responsible for the storage and release of dopamine. In particular, some research has shown DRD2 rs1800497 is mutated or minimized in expression in some Asians (ie, Indian Malaysians), which results in a strong desire for starches, carbohydrates, and fast foods.12-14 Additionally, an MC4R variant has been linked with persons of Asian descent, which appears to render them vulnerable to increased snacking frequency, food addiction,  and/or difficulty with satiety.23-24

DRD2 variant, rs1800497

Dopamine receptor DRD2 – in the expression of polymorphism rs1800497 – affects at least a couple of known health factors in the Asian population25. A 2018 study released in the Journal of Pain Research noted a significant relationship between DRD2 rs1800497 and elevated lipids in a population of Han Chinese subjects 26. More conclusively, in 2018, the Asia Pacific Journal of Clinical Nutrition featured the study of DRD2 Taq1A, Taq1B, and Taq1D gene polymorphisms related to eating behaviors, food cravings, and obesity among Indian Malaysians and Chinese people. Their study noted statistical significance regarding an allele-specific phenomenon of Taq1 polymorphisms which influence eating behaviors of Indian Malaysians. This resulted in increased intake frequency and higher craving of high-fat foods in Indian Malayasian, compared to their Chinese cohort.12 This study, however, called for further exploration of DRD2 in both populations since broader implications regarding obesity remain inconclusive.

 

Yeh et al demonstrated that DRD2 A1 variant for Asians is associated with cravings for carbohydrates and fast foods. The authors suggested that their findings can be extrapolated to a broader Asian population, despite having studied a small sample of Asian-Americans. However, further studies are needed. The study also noted there exists a detrimental chasm between carbohydrate, fast food, and high-fat foods in diets of Asians (specifically Asian females) and a lack of screening for  diabetes and other high risk diseases in this same population10. Hence, there is justification for more attuned health provider screenings. The study  which utilized a blended methodology of questionnaires and blood sample genotyping, showed that the cravings reported in association to DRD2 A1 were carbohydrates and fast food, but not sugar or fat.14 The A1 allele was prevalent in the Asian population studied23. The findings are compelling, but this study is small and the research participants are nutrition students. Thus, further studies on the wider populations are necessary.

 

Finally, earlier detection of possible predisposition to obesity based on factors of emotional eating and association of energy intake issues linked to dopamine expression, have been studied in Chilean groups25; however, inclusive Asian-specific studies are important for public health policy and sound preventative obesity and obesity-related chronic disease protocols.

MC4R variants, Rs12970134 & rs17782313

Eating behaviors cannot be explained by lifestyle and habits alone. The discoveries linked to MC4R variants combat that misperception. 23-24, 27-28Among them, Rs12970134 and Rs17782313 variants are mostly studied in Asian populations when it comes to obesity32-33. A meta-analysis of more than 14000 Indian Asians and Europeans emphasized that Rs12970134 is strongly related to increased waist circumference32. Wang et. al. examined appetite and food intake in overweight and obese Chinese children ages 9-15, focusing on eating behaviors according to the Children Eating Behaviors Questionnaire and rs12979134 genotyping.23 An association arose between appetite (specifically difficulty with satiety) and MC4R responsibility to regulate energy.  A study on Arabic adults indicated that rs17782313 also held a statistically significant risk of obesity13. A loss of functioning variant for gene MC4R, in this same study, indicated weight gain risk.13 These findings are non-isolated, as a 2016 meta-analysis reported a significant relationship between allele B of MC4R rs17782313 and a higher risk of obesity.29 And though the specific mechanisms were inconclusive, Yilmaz, et. al. (2015) studied European ancestry yielding rs17782313 links with mood and eating behaviors, suggesting both further studies between dopamine and obesity, plus Asian specific polymorphism expressions and frequency30.

 

While the potential of an individual’s genetic makeup-based diet is an appealing and intuitive concept in the prevention and management of obesity, particularly among Asians, some limitations should be taken into consideration. Variant interpretation may become challenging because the gene-diet interactions in obesity may be more polygenic. The majority of studies on gene-diet interactions differ in terms of study design, population demographics, and sample size, all of which introduce bias. In particular, some studies on gene-diet interactions have a small population group of Asians and may not be replicated under rigorous conditions. The genotype-diet interaction discovered in one ethnic group may not be more broadly generalizable to other populations. Because genetic variation exists across ancestries and geographical regions, many of these studies should be replicated in other population types. Potential solutions include deriving dietary recommendations from an individual’s ancestral super population or analysing an individual’s genetic file. For future perspectives, more studies, particularly with variants with their high frequencies in super-populations, are necessary to give a better understanding of obesity and weight management for Asians.

Conclusion

Health establishments are at the precipice of genetic understandings of obesity relative to risk and optimal quality of life. Asians have been overlooked in the past for risk connections between genetics, healthy weight, and eating behaviors. Literature calls for Asian specific, region-specific and well rounded research that further explores relationships between genetics, dopamine, energy intake and eating behaviors, which employs psychosocial questionnaires, food diaries, and genotyping). There is a reason to consider genetic testing and ethnic-specific (or inclusive) health care screenings for persons of Asian descent regarding eating behaviors (on par – perhaps, with blood tests for sickle cell disease and Africans and Black Americans). Unique weight concerns such as an elevated risk for Type-2 Diabetes or difficulty in losing weight should be discussed during preventative health care for Asians.

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About the Authors

Anh Nguyen-Hoang, RNT, DCN, CNHC, FBANT

Anh Nguyen-Hoang is a Registered Nutrition Practitioner and Consultant in genomic medicine who works in the intersection of nutrition and genomics to treat and prevent chronic diseases. He serves as Director of Clinical Nutrition at The Edinburgh Children & Women Health Centre, UK. He has been honoured as a Fellow of the British Association for Nutrition and Lifestyle Medicine.  He is also a clinician-researcher at the University of Stirling, UK. His work focuses on patient-oriented research projects on precision nutrition and genomics. He is also known for the efforts to explain profound concepts in personalised nutrition and lifestyle medicine between European and Asian children.  Recently, he is leading a funded research project on nutrition therapy for long COVID. He is also elected for Ambassadorial Scholar to the Genetics Society, one of the oldest learned societies in the UK devoted to genetics, in order to promote education and research on nutritional genomics for healthcare professionals in the UK and Asia. He is a professional member of the Complementary and Natural Healthcare Council, the Association of Genetic Nurses and Counsellors, and the British Society of Genetic Medicine.

With a strong interest in teaching and academic service, he serves as the guest faculty of the European Lifestyle Medicine Organization’s lifestyle medicine certificate programme for medical doctors across the Europe. As Guest Speaker at The Economist, he has participated in workshop series on nutrition, health, and mindfulness for policymakers, healthcare CEOs, and thought leaders across the globe. He has also performed as panel speaker at the Asia Summit Global Health 2021 on public health issues in Asia, organised by The Hong Kong Trade Development Council.

Abdul-Rahman Toufik

Abdul-Rahman Toufik, is a medical student at Sumy State University, Ukraine with a diploma in International Environmental Law and Governance with the “United Nations Environmental Law and Conventions”. He is the CEO and founder of Toufik’s World Organization and Toufik’s World Medical Association. He is also an Associate Editor at the Harvard Public Health Review and a Senior Editor at The Nyc Daily Post.

Wireko Andrew Awuah

Wireko Andrew Awuah holds a Diploma in International Law and Global Governance with the International Business Management Institute, Berlin, Germany. He is a Diplomat who holds several International positions on United Nations platforms. He is recently elected for the Young Scientist Award 2021.

Heather Tillewein

Heather Tillewein is a Harvard Fellow and a Fellow for the California Institute of Integral Studies. She is serving her second term as Communication’s Chair for the LGBTQ Health Caucus for the American Public Health Association. She also serves on the executive committee and on the policy committee for the LGBTQ Health Caucus. She holds a PhD in Health Education from Southern Illinois University. She also has earned her MPH and BSHS from the University of Missouri. Currently, Dr. Tillewein works as an Associate Professor and Program Director for the Undergraduate Public Health program at Southern Illinois University. Her research focuses on health barriers among marginalized sexual identity and gender identity populations. Dr.Tillewein also focuses on sexual health and mental health in her research

Jessica Honig

Jessica Honig, LCSW, Ed.M., Pennsylvania Society for Clinical Social Work, USA. She holds a graduate degree in Arts in Education from Harvard University.

Yves Miel H. Zuniga, FRSPH, AFCHSM, CHM, CPH

Yves Miel H. Zuniga, is the Co-Founder and Deputy Director for Policy and Partnership of MentalHealthPH in the Philippines. As an independent public health consultant, he works in the areas of non-communicable diseases, health policy, and health systems strengthening.

Sailee Bhambere, BDS, MPH

Sailee Bhambere, BDS, MPH, Health Innovators Inc.

Duha Shella

Duha Shella is CEO & Founder of the research community of Palestine “The Researchist”. She is an Elsevier Student Ambassador. Duha is a Student Editor & Palestine Ambassador at the International Journal of Medical Students. Duha is Country Coordinator at the International Youth Alliance for Family planning (IYAFP). She is intern writer at In-Training Magazine. Newly, she got the membership of Committee of Publications Ethics (COPE). She is the General Secretary of Toufik’s World Medical Association. Duha is an MD candidate at An-Najah National University, Palestine. Nationally, Duha, is an ambassador for the Palestinian Forum for medical Research and the third undergraduate Research conference – Al Quds University. Duha is a founder member in Palestinian women in surgery community  in Palestine

Alice Colescu

Alice Colescu is a 3rd year medical student from Romania, Europe. She is a strong communicator on social media, in person, and via email, well-connected within the medical student community. Alice is involved in clubs/organizations on campus and she has a strong med student network community on social media. Extremely detail oriented and hard working, she knows how to collaborate well across departments. Critical thinking, time management, organizational and negotiating skills describe her perfectly. Local Officer of Research Exchange Assistant and Editor-in-Chief of the first Romanian platform for medical admission entry preparation, she also loves playing the piano and paint in her free time. Her life motto: Always have high hopes. Dreams can come true if you have the courage to pursue them.

Candice Carpenter, MD, MBA, MPH, EdM

Candice Danielle Carpenter, MD, MBA, MPH, EdM. Dr. Carpenter serves as Co-Editor-in-Chief of HPHR Journal, and is Founder and Co-CEO of The Boston Public Congress of Public Health.