Gene Mutations that Impact Asians Most Severely
By Najla Zaidi | 23 Jul, 2025

The prevalence of certain key genetic variants within Asian populations have been shown to impact their health in unique ways.

Finding out your personal genetic database can be both exciting and yet cause anxiety and fear, but knowledge is power.  Once you know your own genetic makeup, then you and your physician can formulate an individual plan for you to obtain optimal health.  There are three popular genetic variants that seem to affect Asians in ways that they don’t affect people of other races.  Let’s dive in and see what we should be looking out for.

The Motherf***er Gene

The gene that perhaps has a more frequent impact on everything from mental health to fertility, is MTHFR.  MTHFR is an acronym for a gene in the body, methylenetetrahydrofolate reductase.  The MTHFR gene (sometimes referred to as the "Motherf***er gene") instructs your body to make the MTHFR protein.  This protein helps your body process folate.  Your body needs folate to make DNA and modify proteins.

Like all genes, you have two copies of MTHFR.  Variants on one or both copies mean the resulting MTHFR enzyme is significantly less active, which can impair the body’s ability to process folate and increase levels of the amino acid homocysteine.

MTHFR variants are very common where more people in the United States have one or two variants than don’t, according to the CDC.  C677T and A1298C are two frequently seen polymorphisms of MTHFR.  The polymorphism C677T is the most common in Asia and South America. 

Studies indicate a higher prevalence of the C677T polymorphism in East Asian countries, including China, Korea, and Japan.  However, South Asian countries like India, Pakistan, and Sri Lanka show a lower prevalence.

Studies suggest that people with the C677T MTHFR polymorphism may have lower levels of folate and benefit from supplementation.  Folate deficiency can be the cause of fatigue, weakness, depression, and gastro issues.  Low serum folate levels can lead to dangerously high levels of the amino acid homocysteine, which may cause two issues: increased inflammation, which is linked to a greater risk of heart disease, and impaired function of neurotransmitters (including serotonin, dopamine, and GABA), which is linked to decreased mood and cognitive function. 

The C677T MTHFR mutation is also associated with increased blood pressure and higher total cholesterol, LDL cholesterol and triglycerides.  A 2021 study found these links plus an increase in markers of inflammation, which are all risk factors for cardiovascular disease.  

Studies found links between MTHFR mutations and major depressive disorder, bipolar disorder, and schizophrenia in Asian populations but not Caucasians.  Another study found that the MTHFR C677T polymorphism is associated with Alzheimer’s Disease (AD) in Asian populations, but not in Caucasians. 

It has also been linked to the development of certain types of cancers, including breast cancer, colon cancer, and cervical cancer.  If that’s not bad enough, some evidence has linked MTHFR mutations to recurrent pregnancy loss, male infertility, impaired IVF outcomes and diminished ovarian reserve.  The C677T polymorphism is significantly associated with an increased risk of Preterm Birth (PTB), particularly in Asian and Indian populations.

Additionally, the MTHFR C677T polymorphism is associated with a higher risk of stroke in Chinese adults, particularly intracerebral hemorrhage.  MTHFR activity, associated with increased homocysteine, has been linked to an increased risk of Small Vessel Stroke (SVS) in both East Asian and European populations.

However, MTHFR is actionable. Studies show that getting 400 mcg of folic acid daily can increase blood folate levels, regardless of your MTHFR genotype.

Higher Alzheimer's Risk

Research has shown that changes in certain genes can increase a person’s risk of developing Alzheimer's Disease (AD), per the National Institute on Aging.  The strongest known genetic risk factor for AD is a form of the apolipoprotein E (APOE) gene called APOE ɛ4.  APOE helps carry cholesterol and other fats in the bloodstream, and issues in this process can contribute to AD.

The most common APOE alleles are the ε2, ε3, and ε4 alleles, which were discovered to each be associated with varying levels of risk for AD.  However, the ε4 allele has been confirmed to be a major risk factor for AD whereas the ε2 allele has been shown to be protective.  A growing body of evidence suggests that APOE ɛ4 carriers experience accelerated brain atrophy, even in the absence of cognitive impairment.

The proportion of APOE ɛ4 carriers is lower in the Asian population than in the European population.  However, the impact of APOE ɛ4 on dementia development is more pronounced in the Asian population.  Notably, the ε4 allele has a stronger effect in East Asian populations specifically as compared to other populations. 

A study showed that the APOE ε4 allele led to an increased rate of cognitive function decline in Han Chinese in Taiwan.  Studies on APOE and dementia incidence in Japanese American populations have also been conducted as part of the Honolulu-Asia Aging Study (HAAS).  The study confirmed that association between APOE alleles and AD. 

The Sprinter Gene

The ACTN3 gene affects the deficiency and muscle type a person has.  The ACTN3 gene, often referred to as the "sprinter gene", plays a part in the production of α-actinin-3, a protein found in fast-twitch muscle fibers responsible for generating forceful, high-velocity contractions.  The R577X polymorphism in the ACTN3 gene leads to three genotypes: RR, RX and XX. 

The frequency of the α-actinin-3 deficient genotype (577XX) varies significantly among ethnic groups, with approximately 25% in Asian populations compared to less than 1% in an African Bantu population, and around 18% in Europeans.  The absence of α-actinin-3 (XX genotype) is generally underrepresented in sprint and power-based sports.

The presence of the R allele and the RR genotype is often associated with better sprint/power performance.  Studies in elite Chinese and Japanese athletes have shown a higher frequency of the RR genotype among sprinters and power athletes compared to controls or endurance athletes. 

Conversely, the XX genotype has been associated with endurance performance, with studies suggesting that the absence of α-actinin-3 might provide an advantage for endurance athletes.  For example, one study found a significantly higher frequency of the ACTN3 XX genotype and X allele in female endurance athletes in China compared to controls.

Some research indicates that the R allele may be associated with increased muscle thickness in response to resistance training.  Additionally, studies have linked the RR genotype to higher grip strength in Chinese male soldiers.

Emerging evidence suggests that the XX genotype might predispose individuals to a higher risk of certain non-contact injuries, such as muscle injuries and ankle sprains, and lead to higher levels of exercise-induced muscle damage.  However, some studies have presented conflicting data, with research indicating that XX individuals may recover faster after muscle-damaging exercise.

Genetic information alone is not a definitive predictor of athletic success or injury susceptibility.  Environmental factors like training and nutrition also play a crucial role. 

Knowing your genes can help you lower your disease risk, improve metabolic health, and overhaul your mental health.