Introduction: The era of genetic testing and personalized healthcare
In recent years, genetic testing has become increasingly common in the fields of medicine and health management. Advances in DNA analysis technology have made it possible to easily check an individual’s genetic information, leading to applications in many areas, including assessing disease risk, selecting appropriate medications, and optimizing diet and exercise.
In particular, personalized healthcare has been attracting attention, and the use of genetic information will enable more precise health management. This article will take a detailed look at the types of genetic testing, technological advances, use cases, and ethical issues.
Types and Purposes of Genetic Testing
Genetic testing is carried out for three main purposes:
1. Diagnostic Genetic Testing
This test is used to diagnose a disease that already has symptoms, in order to determine whether a specific gene mutation is the cause of the disease and to determine the course of diagnosis and treatment.
Example: Hereditary breast cancer (BRCA1/BRCA2 gene mutations)
It is useful in diagnosing hereditary breast and ovarian cancer syndrome (HBOC).
If a BRCA gene mutation is present, surgery or preventive treatment may be considered.
Example: Muscular dystrophy (DMD gene mutation)
It is used to definitively diagnose Duchenne muscular dystrophy.
2. Predictive Genetic Testing
This test is used to assess the risk of developing a disease in people who do not yet have symptoms.
Example: Alzheimer’s disease (APOE gene)
People with the APOE4 allele are at increased risk of Alzheimer’s disease.
Example: Type 2 diabetes (TCF7L2 gene)
People with certain polymorphisms are at higher risk of developing diabetes and are recommended to improve their lifestyle habits.
3. Pharmacogenetic testing (pharmacogenomics)
This test predicts the effectiveness of medicines, and the risk of side effects based on genetic information. It helps to select the most suitable medicine for each individual and realizes safer and more effective treatment.
Example: Warfarin (anticoagulant) and the CYP2C9 gene
Because there are genetic differences in how quickly people metabolize warfarin, genetic testing is used to determine the appropriate dosage.
Example: Anticancer drug (irinotecan) and the UGT1A1 gene
The risk of side effects from anticancer drugs varies depending on UGT1A1 gene polymorphisms.
Latest technology and evolution of genetic testing
Technologies supporting the spread of genetic testing include next-generation sequencing (NGS) and DNA microarray analysis.
1. Next Generation Sequencing (NGS)
NGS technology can analyze large numbers of DNA sequences simultaneously, making it possible to read genetic information more quickly and accurately than conventional methods, which has led to major advances in cancer genome analysis and the diagnosis of rare diseases.
2. DNA Microarray Analysis
This is a method for comprehensively analyzing polymorphisms in specific genes and is used for disease risk assessment and ancestry analysis. This technology is also widely used in consumer genetic testing services.
Examples of genetic testing
1. Cancer genomic medicine
“Precision medicine” is being practiced, in which genetic mutations in cancer patients’ tumor cells are analyzed and the most appropriate molecular targeted drug is selected.
Example: Detection of EGFR gene mutations in lung cancer patients and selection of molecular targeted drugs.
2. Prevention of lifestyle-related diseases
By utilizing genetic testing, it is possible to manage health according to individual risks.
Example: A person at high risk for high blood pressure or high cholesterol receives diet and exercise advice.
3. Sports Genetics
We examine genes related to muscle type and recovery ability and design training that suits each individual’s abilities.
Example: Polymorphisms in the ACTN3 gene are one of the factors that determine whether someone is better suited to sprinting or endurance running.
Challenges and ethical issues of genetic testing
As genetic testing becomes more widespread, ethical and social issues have also been raised.
1. Genetic Information Privacy and Data Management
Genetic information is highly confidential data for individuals and is at risk of being improperly managed or leaked.
For example, genetic information could be misused by insurance companies and employers.
2. Psychological impact of test results
Genetic test results may increase anxiety about future health risks.
For example, the psychological burden of being told that you are at high risk for Alzheimer’s disease.
3. Genetic Discrimination
The possibility that individuals with certain genetic risks may be disadvantaged in insurance and employment situations.
Although some countries have enacted the Genetic Information Nondiscrimination Act (GINA), international rules need to be established.
Research findings and evidence
Below is an example of a study showing the effectiveness of genetic testing.
The New England Journal of Medicine (NEJM, 2018) : “BRCA gene mutations and breast cancer risk”
論文リンク
Nature Genetics (2021) : “Pharmacogenetic testing may reduce drug side effects”
Genetic testing and nutrition: personalized nutrition
Genetic testing makes it possible to provide personalized nutrition based on an individual’s genetic makeup. Research has shown that certain gene mutations affect vitamin and mineral metabolism, lipid processing, appetite regulation, and more.
1. Relationship between nutrient metabolism and genes
By understanding how your individual genes affect how you absorb and metabolize nutrients, you can create more effective dietary choices.
The MTHFR gene and folate metabolism
If you have a specific polymorphism (C677T) in the MTHFR gene, your body’s ability to metabolize folic acid is reduced, making you more likely to have elevated homocysteine levels.
Because hyperhomocysteinemia is a risk factor for cardiovascular disease, it is recommended to consume foods rich in folate (such as spinach and avocado).
The FTO gene and obesity risk
People with certain mutations in the FTO gene tend to have a higher-than-normal appetite and become more prone to obesity.
If this mutation is identified through genetic testing, strategies to curb weight gain such as food portion control and a high-protein diet are considered effective.
APOA5 gene and lipid metabolism
People with a mutation in the APOA5 gene are more likely to have high levels of triglycerides (neutral fats) in their blood.
This increases the risk of arteriosclerosis, so a diet low in fat and high in omega-3 fatty acids is recommended.
Genetic testing and sports science: potential for improved performance
Advances in sports genetics have made it possible to assess an individual’s athletic ability and aptitude using genetic testing. Understanding their genetic characteristics allows athletes to tailor their training programs to best suit their needs.
1. Muscle fiber type and the ACTN3 gene
The ACTN3 gene is involved in fast-twitch muscle fibers (muscles that require explosive force).
Depending on the ACTN3 R577X genotype, it is classified into three types: endurance type (X/X), sprint type (R/R), and intermediate type (R/X).
R/R blood types are better suited to sprinting and weightlifting, while X/X blood types are better suited to long-distance running and endurance sports.
2. Lactate metabolism and the PPARGC1A gene
The PPARGC1A gene affects energy metabolism and the ability to remove lactate in muscles.
People with the mutation may be better adapted to endurance training.
3. Injury risk and the COL5A1 gene
The COL5A1 gene is involved in collagen synthesis, affecting the strength of tendons and ligaments.
People with certain gene mutations are at higher risk of ligament injuries and Achilles tendon ruptures, so flexibility-focused training is recommended.
Genetic testing and mental health: assessing risk for mental illness
Genetic testing is also beginning to be used to assess the risk of mental illnesses such as depression, anxiety disorders, and schizophrenia.
1. Depression and the 5-HTTLPR gene
5-HTTLPR is a gene involved in the serotonin transporter and influences mood regulation.
People with the S allele tend to have lower stress tolerance and a higher risk of depression.
The application of stress management and cognitive behavioral therapy (CBT) is said to be effective.
2. Dopamine and the DRD2 gene
The DRD2 gene influences the sensitivity of dopamine receptors.
People with the mutation may be more likely to have activated reward systems, putting them at higher risk of addiction.
It can also be used to evaluate eating, gambling, and alcohol addiction.
3. Sleep patterns and the CLOCK gene
The CLOCK gene regulates the circadian rhythm (body clock).
People with the mutation are more likely to suffer from insomnia and seasonal affective disorder (winter depression).
The habit of going to bed early and getting up early, as well as light therapy, are said to be effective.
Current status and challenges of consumer genetic testing
The widespread availability of genetic testing has made it easy for individuals to learn their own genetic information. However, it has also highlighted issues regarding the interpretation of test results and data management.
1. Widespread availability of commercially available genetic testing kits
Direct-to-consumer genetic tests offered by companies such as 23andMe and AncestryDNA are gaining popularity.
Ancestry analysis and physical constitution diagnosis are possible, but disease risk assessment may not be medically backed up.
2. Data Privacy and Security
There are concerns that there is a risk of genetic information being leaked or misused.
Some companies may share their customers’ genetic data with third parties (such as pharmaceutical companies).
3. Legal and ethical issues
There are efforts to prevent the misuse of genetic information through legal regulations such as GINA (Genetic Information Nondiscrimination Act), but the progress of legal developments varies from country to country.
The issue of “genetic discrimination” by insurance companies and employers is being discussed.
Genetic testing and infectious disease risk: individual differences in the immune system
It is known that genes also affect immune responses to viruses and bacteria. Because specific gene mutations affect susceptibility to infectious diseases and the risk of developing severe symptoms, genetic testing can help determine more appropriate preventive measures.
1. COVID-19 and genetic factors
Research has shown that multiple genes are involved in the immune response to the new coronavirus (SARS-CoV-2).
HLA genes and risk of severe COVID-19
HLA (human leukocyte antigen) genes play an important role in helping the immune system recognize viruses.
Certain HLA polymorphisms (e.g., HLA-B*46:01) have been reported to increase the risk of severe COVID-19.
On the other hand, people with HLA-B*15:03 may have greater protection against the virus.
ACE2 gene and viral infection
The ACE2 receptor serves as the gateway through which the new coronavirus enters cells.
Different variants of the ACE2 gene may affect the susceptibility of the virus to infection.
TMPRSS2 gene and viral proliferation
TMPRSS2 is a gene that encodes an enzyme that activates the viral spike protein.
It has been suggested that genetic variations may affect susceptibility to infection and the severity of symptoms.
2. Influenza viruses and immune responses
IFITM3 gene and influenza severity
The IFITM3 gene plays a role in preventing viruses from entering cells.
It has been reported that the presence of a specific variant of IFITM3 (rs12252-C) increases the risk of pneumonia after influenza infection.
TLR genes and innate immunity
Toll-like receptors (TLRs) function as pathogen sensors in the body.
Mutations in the TLR7 gene are associated with an increased risk of viral infections.
3. HIV (Human Immunodeficiency Virus) and Genetic Resistance
CCR5-Δ32 mutations and HIV resistance
It has been confirmed that people with the CCR5-Δ32 mutation have a harder time getting HIV to enter cells and become infected.
The proportion of people with this mutation is higher in Northern European populations.
Genetic testing and aging: genetic factors that determine lifespan
Genetics plays a major role in how long you live and how quickly you age, and genetic testing can help identify genetic traits that are associated with longevity
1. Telomere length and the TERT gene
Telomeres are structures at the ends of chromosomes that shorten with each cell division.
The TERT (telomerase reverse transcriptase) gene is involved in maintaining telomeres, and people with certain variants are believed to be more likely to live longer.
Proper diet, exercise, and stress management are important for maintaining telomere length.
2. FOXO3 gene and longevity
The FOXO3 gene is involved in cellular resistance to oxidative stress and DNA repair ability.
Studies have shown that people with certain variants of FOXO3 are more likely to live to be over 100 years old.
A high frequency of this gene variant has also been confirmed in a long-lived population in Okinawa.
3. SIRT1 gene and anti-aging
SIRT1 is a gene that encodes a longevity-related protein called sirtuin.
High activity of the SIRT1 gene may slow the rate of aging.
Resveratrol, a polyphenol found in red wine, is known to activate SIRT1.
Genetic testing and allergies: individual differences in immune response
Allergies develop as a result of interactions between heredity and the environment, and it is known that genetic factors play a major role. Genetic testing makes it possible to evaluate the risk of allergic diseases and take preventive measures.
1. Hay fever and HLA genes
It has been reported that variants of the HLA-DQ gene are associated with the risk of developing cedar pollen allergy.
If genetic testing indicates a high risk, allergen immunotherapy can be considered early on.
2. Food allergies and genetic susceptibility
It has been reported that mutations in the IL-4R gene increase the risk of developing peanut allergies.
Polymorphisms in the IL-13 gene are associated with risk of asthma and allergic rhinitis.
3. Atopic dermatitis and the FLG gene
Mutations in the FLG (filaggrin) gene reduce the skin’s barrier function and increase the risk of developing atopic dermatitis.
By utilizing genetic testing and using skin care products that strengthen the barrier function, it is possible to prevent symptoms from worsening.
Genetic testing and gut bacteria: Individual differences in gut flora and their impact on health
Intestinal bacteria (intestinal flora) are deeply involved in the human digestive function and immune system, and their composition is determined in part by genetic factors. In recent years, research has been progressing to optimize the intestinal environment by analyzing the relationship between genetic testing and intestinal bacteria, leading to improved digestive disorders and immune function.
1. Genetic influences on gut flora
It is known that the types and balance of intestinal bacteria tend to be determined by genes.
LCT gene (lactase gene): Determines the risk of lactose intolerance and influences the ability to digest dairy products.
FUT2 gene: Involved in the establishment of bifidobacteria in the intestines and determines the health of the intestinal environment.
2. Interaction between genes and gut flora
People with certain genotypes tend to have more of certain gut bacteria.
For example, people with more Prevotella bacteria are able to digest carbohydrates more efficiently, whereas people who prefer a meat-based diet tend to have more Bacteroides bacteria.
By conducting genetic testing of intestinal bacteria, it is possible to select the optimal diet and improve the intestinal environment.
3. Relationship between intestinal flora and disease risk
The relationship between obesity and intestinal flora : Obese people tend to have more Firmicutes bacteria and fewer Bacteroidetes bacteria.
Inflammatory bowel disease (IBD): Genetic mutations (such as the NOD2 gene) disrupt the balance of intestinal bacteria, increasing the risk of Crohn’s disease and ulcerative colitis.
Link to mental illness: The gut flora also affects mental health through the brain-gut axis and has been shown to be associated with depression and anxiety disorders.
Genetic testing and skin type: personalizing skin care
Skin type and the rate at which it ages are influenced by both genetic and environmental factors, and genetic testing can help you make skin care choices that are best suited to you.
1. Collagen production and the MMP1 gene
The MMP1 gene codes for an enzyme that breaks down collagen, and people with certain mutations are more likely to experience premature skin aging.
To suppress collagen breakdown, it is effective to take antioxidants (vitamin C, resveratrol).
2. UV resistance and the MC1R gene
Mutations in the MC1R gene determine the skin’s ability to produce melanin and its resistance to ultraviolet rays.
People with UV-sensitive genotypes are more susceptible to sunburn and have a higher risk of skin cancer, so a high SPF sunscreen is recommended.
3. Risk of wrinkles and age spots and the SOD2 gene
The SOD2 gene encodes an enzyme that breaks down reactive oxygen species and affects the skin’s resistance to oxidative stress.
If you have genetically low SOD2 activity, your skin is more likely to age, so antioxidant care is important.
Genetic testing and smell/taste: genetic factors determining food preferences
Research has shown that our sense of smell and taste are genetically determined, and that certain genetic variants influence our food preferences.
1. Bitterness perception and the TAS2R38 gene
Variants in the TAS2R38 gene affect how bitterness is perceived.
“Supertasters” (those who have a strong sense of bitterness) tend to dislike broccoli and coffee.
2. Sweet taste sensitivity and the SLC2A2 gene
The SLC2A2 gene influences sweetness sensitivity and determines the tendency to consume sugar.
People who are sensitive to sweet tastes tend to consume less sugar.
3. Umami receptors and the T1R1/T1R3 genes
Sensitivity to umami (glutamic acid) is determined by polymorphisms in the T1R1/T1R3 genes。
People who have a strong sense of umami tend to like kelp and fermented foods.
Genetic testing and alcohol tolerance: Genes that determine the effects of drinking
The ability to break down alcohol varies from person to person, and genetic factors play a large role. Genetic testing can provide a more accurate understanding of the effects of alcohol.
1. ALDH2 gene and alcohol decomposition ability
The ALDH2 gene encodes an enzyme (acetaldehyde dehydrogenase) involved in the metabolism of alcohol.
People with low ALDH2 activity are more likely to have acetaldehyde accumulate in their bodies, causing facial flushing and hangovers after drinking alcohol.
If there is no ALDH2 activity at all (homozygous mutation), alcohol cannot be broken down, so drinking alcohol should be avoided.
2. ADH1B gene and susceptibility to motion sickness
The ADH1B gene encodes an enzyme that converts alcohol to acetaldehyde.
When ADH1B activity is high, alcohol is broken down quickly, making the effects of drinking more apparent in a short period of time.
3. The relationship between alcohol and cancer risk
It has been reported that people with inactive ALDH2 genes are at higher risk of alcohol-related esophageal and head and neck cancer.
By undergoing genetic testing, you can understand your own alcohol metabolism ability and establish appropriate drinking habits.
Genetic testing and caffeine sensitivity: How quickly we metabolize caffeine
While caffeine has the effect of increasing concentration and waking you up, depending on the amount consumed it can also cause insomnia and an increased heart rate. One of the reasons why the effects of caffeine vary from person to person is related to differences in metabolic rates due to genetic differences.
1. Caffeine metabolism and the CYP1A2 gene
The CYP1A2 gene encodes an enzyme responsible for the metabolism of caffeine.
People who are “rapid metabolizers (AA type)” are able to break down caffeine quickly, so the effects wear off quickly.
People who are “slow metabolizers (AC and CC)” have a higher risk of sleep disorders and palpitations because caffeine stays in their bodies longer.
2. Caffeine intake and health risks
Research has shown that high caffeine intake in slow metabolizers increases the risk of high blood pressure and heart disease.
Conversely, for fast metabolizers, moderate amounts of caffeine may help improve endurance and cognitive function.
Genetic testing can help you determine your caffeine sensitivity and adjust your intake accordingly.
Summary
Genetic testing is revolutionizing all areas of medicine, health management, and lifestyle. It can be applied in a wide range of ways, including predicting disease risk, selecting optimal medications, and personalizing nutrition, exercise, and skin care. In particular, understanding individual genetic characteristics can improve the accuracy of preventive medicine and health maintenance, allowing for more effective measures. At the same time, attention must be paid to privacy protection and ethical issues. As science advances, it is important to use genetic information correctly.
