World of Genomics: Vietnam

In our latest World of Genomics piece, we travel to Vietnam, a country known for its rich culture, delicious food and beautiful landscapes. With one of the fastest growing economies in Southeast Asia, Vietnam is becoming one to watch in the field of genomics. 

The population of Vietnam

Vietnam is located in Southeast Asia, at the eastern edge of the Indochinese Peninsula. Since humans first settled in Mainland Southeast Asia around 65,000 years ago, extensive migration has occurred across the area, resulting in modern-day Vietnam having a very diverse population. Vietnam is home to 54 ethnic groups and has remarkable ethnolinguistic diversity, with over 110 languages spoken in the country. This diversity makes Vietnam a very interesting population to study genetically. However, Vietnam’s genetic diversity to date has been the focus of very few genetic studies.

After invasion by the French in 1858, Vietnam eventually became part of French Indochina in 1887. The French rule continued until their defeat by communist forces in 1954. This resulted in a split nation – the communist North and the anti-communist South. The tension between the two states ultimately led to the Vietnam War in 1955, which lasted nearly 20 years. The Fall of Saigon in 1975 marked the end of the war and the reunification of the country into the Socialist Republic of Vietnam.

Despite the end of armed conflict, Vietnam continued to suffer from the effects of war for many years after. Conservative leadership policies and the mass emigration of South Vietnamese individuals, including successful merchants, resulted in Vietnam becoming internationally isolated. It wasn’t until 1986, when a series of free-market reforms were enacted, that the Vietnamese economy was able to develop and grow. Since then, the science and technology industry has blossomed, with the number of Vietnamese scientific publications steadily increasing.

Geographic and demographic information

Summary statistics:

• Land area: 310,070 km²
• Gross domestic product (GDP):
  • Total: $271.2 billion
  • Per capita: $2,785

Population statistics:

• Population size: As of July 2021, the population of Vietnam was estimated to be 102,789,598.
• Birth rate: In 2019, the crude birth rate was 16.45 births per 1,000 people.
• Death rate: In 2019, the crude death rate was 6.38 deaths per 1,000 people.
• Infant mortality rate: In 2019, the infant mortality rate was 15.9 per 1,000 live births.
• Average life expectancy: The average life expectancy at birth in 2021 is 75.25 years.
• Ethnicity: The major ethnic group in Vietnam is the Kinh (Viet) group, which comprises 85.3% of the population. Other minority groups include Tay (1.9%), Thai (1.9%), Muong (1.5%), Khmer (1.4%), Mong (1.4%) and Nung (1.1%). The Vietnamese government currently recognises 54 ethnic groups in total.

Healthcare system

Vietnam currently has a unique mixed public-private healthcare system but is striving towards implementing universal healthcare. Healthcare expenditure has been steadily increasing and is forecast to triple from $15.6 billion in 2018 to $42.9 billion in 2028.

Today, the public healthcare system, the largest part, is organised into four levels of service delivery: (1) central level (regional hospitals and research institutes), (2) provincial and district levels, (3) commune level and (4) a network of village health workers who make house calls. There are also two-track systems at each level. One focuses on prevention and mother and child healthcare, and the other is devoted to clinical acute care.

Social health insurance, which was established in 1992, is the main method of public financing for healthcare in Vietnam. Almost all preventative services, such as immunisations and mother and child-care, are free. However, a fee is charged for all other services. As of 2018, 87% of the Vietnamese population were covered by social health insurance. Currently, the government subsidises 100% of healthcare fees for the poor, ethnic minority groups, war veterans, children under six and the elderly over 80 years old. In addition, the government provides a 30% subsidy to groups including pupils in elementary school and workers in the agriculture, forestry and fishery sectors who make average incomes.

Despite these subsidies, the cost of healthcare remains a problem. Out-of-pocket payments still account for approximately 41% of total health expenditure, pushing many families into poverty. The quality of care is usually very high in private hospitals. However, public district hospitals, especially those in rural areas, suffer from underfunding and lack of equipment. This results in patients travelling to larger regional hospitals instead, leading to overcrowding. Improving the use and efficiency of social health insurance is therefore a top priority for the Vietnamese government.

Health priorities

Cardiovascular diseases are the leading causes of death in Vietnam, accounting for 31% of deaths in 2016. Strokes specifically cause the most deaths, followed by ischemic heart disease. Additionally, the incidence of diabetes is rapidly rising. Between 2006 and 2016, diabetes cases doubled. This is due to rapid urbanisation and globalisation within Vietnam. The recent entrance of fast-food chains into the country has contributed to a shift from the traditional Vietnamese diet, which is low in meat and high in vegetables, to an unhealthier Westernised diet. As a result, the Ministry of Health launched a major health awareness campaign in 2015 to combat this, alongside a programme to improve access to diabetic services.

In addition, several health defects in the Vietnamese population are related to the use of dioxin, also known as Agent Orange. US military forces used dioxin as a defoliant during the Vietnam War. However, dioxin is now considered a carcinogen. Despite the war ending 46 years ago, dioxin is still found in Vietnamese individuals today. Dioxin levels remain high in the breast milk of mothers residing near heavily contaminated areas, resulting in varied health effects on subsequent generations. For example, perinatal exposure to dioxin adversely affects both infant neurodevelopment and children’s learning abilities. Even individuals who do not live in dioxin hotspots have been found to still consume dioxin through contaminated food.

Like most countries, one of the biggest healthcare challenges in Vietnam is a rapidly ageing population. According to the United National Population Fund (UNFPA), Vietnam’s population entered the ‘ageing phase’ in 2011. It is expected that by 2050, 28% of the Vietnamese population will be over 65 years old. As a result, there has been a sharp shift from communicable to noncommunicable diseases (NCDs), such as dementia and cancer. In fact, mortality from NCDs increased from 45.5% in 2010 to 77% in 2016. Reforms will need to be made to the current healthcare system to ensure that these challenges are met head on.

Genomic medicine capabilities

Despite having the 15^th largest population in the world, Vietnam has been severely under-represented in genetic databases and studies until fairly recently. In fact, there was only one dataset of 99 Vietnamese individuals that had been studied as part of the 1000 Genomes Project. This under-representation has hindered the implementation of genomic medicine. However, the falling costs of genome sequencing and genetic testing has enabled further growth in this field.

Prenatal diagnostic services in Vietnam have developed quickly, although they were only introduced in 2007. Non-invasive prenatal testing (NIPT) is now well established and a standard screening procedure for pregnant Vietnamese women. The screening is able to detect trisomies 21, 18 and 13 with over 99% accuracy.

More than 12 million Vietnamese people carry the genetic variant that causes thalassemia, a recessive genetic blood disorder. The genetic frequency of thalassemia is particularly high in Vietnam. Carrier rates vary from 1.5% up to 25% in certain ethnic groups. In comparison, approximately 0.44% of the population in England carry the mutation. Despite this, Vietnam does not currently offer routine genetic testing for thalassemia. However, in May 2021, a pilot project began to screen pregnant women for this disorder. This is the first scientific study in Vietnam to use next generation sequencing (NGS) technology to screen for thalassemia. If the method deployed is found to be effective, the screening will be rolled out on a much wider scale.

Although progress is being made in terms of genetic testing, there is still more to be done. As of 2018, there were approximately 13 trained medical geneticists in Vietnam for a population of over 90 million. In addition, genetic counselling services are available but are very limited. Cytogenetic and molecular laboratories also exist, but often only have access to limited technologies. Whole genome and whole exome sequencing, for example, are also not yet routinely available for clinical care.

Notable projects

• The 1000 Vietnamese Genome Project (1KVG): 1KVG is the first large-scale human whole genome sequencing project in Vietnam. VinGroup’s Institute of Big Data is carrying out the project. It began in 2019 and is expected to finish in 2024. The project is comprised of two phases – the first will sequence and analyse samples, and the second will use the findings to develop new testing methods for diseases and drug side effects. The researchers will compile the findings into a database accessible to global research communities.
• Không Thalassemia: “Không Thalassemia”, which translates as “Thalassemia Free”, is a joint project between Gene Solutions and the Medical Genetics Institute. The project began in May 2021 and will last for six months, after which the findings will be evaluated. The researchers hope that, in the future, screening for thalassemia will be available for all pregnant women as well as couples planning to have children. Gene Solutions say that the test will be free for those who don’t have the means to pay.
• Vietnamese human genetic variation database: This genetic database contains data from 406 Kinh (Viet) individuals. Researchers from the Vinmec Research Institute of Stem Cell and Gene Technology carried out the project in 2019. The database contains 24.81 million variants, of which 710,000 are novel. In addition, 107 of the variants were identified as pathological mutations with a frequency above 1% in the Kinh population. The database is available to view online.
• Reconstructing the Vietnamese genetic profile: This was a 2020 study by Vietnamese researchers who used NIPT data to reconstruct the genetic profile of the Vietnamese population. Their results, which revealed genetic variants for prevalent genetic disorders in Vietnam, highlighted the need for population-specific genome-wide association studies. A database of the identified genetic variants is available online and will serve as a valuable resource for future studies.

Several projects have also explored the genetic diversity between the many ethnic groups within Vietnam. For example, researchers have shown that Vietnamese ethnolinguistic groups harbour multiple sources of genetic diversity. One project also found that there is substantial genetic diversity that is not represented by the Kinh group alone. Interestingly, studying minority ethnicities can also reveal historical demographic movements. These projects highlight the importance of studying minority ethnic groups.

Notable organisations and companies

• Vinmec Research Institute of Stem Cell and Gene Technology (VRISG): VRISG was established in October 2016 by Vinmec, a non-profit health system developed by Vingroup, the largest conglomerate of Vietnam. VRISG have carried out many important genomic studies. These include building a Vietnamese human genetic variation database and discovering novel genes linked to autism spectrum disorder in Vietnamese children.
• Gene Solutions: Established in Ho Chi Minh City in 2018, Gene Solutions develops genetic testing solutions for diagnosing diseases. The company also performs non-invasive prenatal screening for pregnant Vietnamese women, using a unique procedure known as triSure developed by Vietnamese scientists in 2018.
• Medical Genetics Institute: Founded in 2010, the Medical Genetics Institute in Ho Chi Minh City is a privately funded genetics research institute. The Institute carries out affordable prenatal screening, as well as carrying out real-time sequencing.
• VinGroup Institute of Big Data: Founded in August 2018, the Institute is carrying out the 1000 Vietnamese Genome Project. VinGroup has invested $4.5 million in the sequencing project. The data collected so far is already available to view online.
• Oxford University Clinical Research Unit (OUCRU): OUCRU is a large-scale clinical and public health research unit based within the Ho Chi Minh City Hospital for Tropical Diseases. Established in 1991, OUCRU focuses on significant infectious diseases. As part of their work, they investigate host genetics underlying susceptibility to disease.
• Vietnam Medical Genetics Association: The Vietnam Medical Genetics Association was officially established by the Ministry of Home Affairs in April 2019. It is a professional association of geneticists and doctors with the aim of developing national medical genetics.
• Office of Genetic Counselling & Disabled Children (OGCDC): The OGCDC is a local nongovernment association and charity located in Hue, Central Vietnam which provides genetic counselling services to disabled children and their families.
• National Institute of Forensic Medicine: A branch of the Ministry of Health, the National Institute of Forensic Medicine carries out genetic testing and analysis. Although the Institute previously faced difficulties due to lack of equipment, they have recently acquired next generation sequencing technology.

Notable individuals

• Nguyễn Phúc Bửu Hội (1915-1972): Nguyễn Phúc Bửu Hội was a Vietnamese scientist who primarily worked in France. His work, which mainly focused on carcinogenesis, established him as an international authority in chemotherapy. He received multiple awards from the French National Institute of Health and Medical Research for his work in cancer research.
• Võ Đình Tuấn (1948-): Professor Võ Đình Tuấn is a Professor at Duke University. He pioneered the development of a new generation of gene biosensing probes. The probes allow for multiplex and label-free detection of nucleic acid biomarkers in early detection of a wide range of diseases. Currently, his research group is developing photothermal immunotherapy technology that uses lasers and gold nanostars to heat up and destroy tumours.
• Nguyễn Thanh Liêm (1952-): Professor Nguyễn Thanh Liêm is the director of VRISG and was the head of the “Vietnamese human genetic variation database” project. He is a pioneer and innovator in paediatric endoscopic surgery and stem cell transplantation for diseases such as autism, cerebral palsy and liver cirrhosis for children in Vietnam.  
• Vũ Hà Văn (1970-): Professor Vũ Hà Văn is the director of VinGroup’s Institute of Big Data and a Professor at Yale University. Although he is a mathematician by training, he is now leading the 1000 Vietnamese Genome Project.

Next steps

The lack of Vietnamese genomes in databases has meant that previous genetic studies for Vietnamese people has mostly relied on genetic information from other populations. Therefore, studying the Vietnamese population directly is incredibly important to uncover any unique genetic variants and diseases. As sequencing costs continue to fall, Vietnam has been able to implement more genomic technologies. As such, this is becoming a very exciting time for Vietnam in the field of genomics.

The ongoing 1000 Vietnamese Genome Project (1KVG) is proof of Vietnam taking matters into their own hands and actively investing in genomic projects. The results of 1KVG will provide a much-needed database of Vietnamese genomic information, which will hopefully pave the way for the implementation of precision medicine in the country.

However, Vietnam still has many steps to take in order to establish themselves in the genomics field. Most notably, there is still limited access to many advanced technologies. It is hoped that partnerships with other countries will help develop the required infrastructure. For example, since 2007, Vietnamese geneticists have been collaborating with American and Canadian geneticists. This collaboration is continually providing educational support, genetic counselling and clinical and molecular diagnostic expertise to Vietnamese researchers.

In addition, increased public education is required. Studies have shown that Vietnamese women with higher educational attainment are more likely to undergo prenatal screening for genetic disorders. Meanwhile, women from disadvantaged backgrounds often do not understand what the screening involves or what it is for, putting them off from using these services. Differences between traditional practices and modern clinical methods can also act as a barrier to individuals, particularly ethnic minority patients, seeking out genetic services. Public engagement on these issues will be needed to overcome these challenges.

Despite this, many of the current organisations concentrated on genetic research are relatively new and it is clear that the Vietnamese government is supportive of genomic projects. It will be very exciting to watch how Vietnam’s genomic industry continues to develop over the next few years!

References

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• Dang, Thu Ha, et al. “Patient-Centered Care: Transforming the Health Care System in Vietnam With Support of Digital Health Technology.” Journal of medical Internet research 23.6 (2021): e24601.
• Tran, Ngoc Hieu, et al. “Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data.” Scientific reports 10.1 (2020): 1-8.
• Phan, Minh-Duy, et al. “Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam.” The Journal of Maternal-Fetal & Neonatal Medicine 32.23 (2019): 4009-4015.
• Ha, Bui Thi Thu, Nguyen Thi Thu Huong, and Doan Thi Thuy Duong. “Prenatal diagnostic services in three regional centers in Vietnam.” International journal of public health 62.1 (2017): 27-33.
• Nguyen, Tuyet Thi, and Maurizio Trevisan. “Vietnam a country in transition: health challenges.” BMJ Nutrition, Prevention & Health 3.1 (2020): 60.
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