The evaluation of kidney filtration is the central point of diagnosing chronic kidney disease classification (CKD). The effects of methionine metabolism and total homocysteine levels have a strong association with decreased glomerular filtration rate (GFR). Furthermore, the enzymes and cofactors involved in the methionine metabolism process are crucial in maintaining homocysteine (tHcy) levels. Therefore, the methylenetetrahydrofolate reductase (MTHFR) enzymatic function is essential to modulate tHcy and increase GFR. Nowadays, detecting single nucleotide polymorphisms (SNPs) in MTFHR is a key determinant to assess CKD and prevent co-morbidities like stroke and coronary heart disease.
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Methylenetetrahydrofolate reductase (MTHFR) is the catalytic enzyme that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Consequently, this causes the remethylation of homocysteine to methionine. The recycled homocysteine is reused to build other proteins, and vitamins like folate, cobalamin, and pyridoxine serve as cofactors that modulate MTHFR function. However, genetic mutations in the MTHFR can provoke a non-optimal functionality of such an enzyme and result in elevated homocysteine levels.
Genetic Mutations in the MTHFR gene
Our parents commonly inherit genetic mutations. Every patient inherits two MTHFR genes, and if only one of their MTHFR genes is mutated, this patient is considered heterozygous. However, if both of their genes present the mutation, this patient is deemed to be homozygous.
The SNP C->T at nucleotide position 677 results in a codon substitution that leads to an Ala-> Val amino acid change. Furthermore, this amino acid change is associated with hyperhomocysteinemia, linked to neural tube defects, coronary heart disease, depression, schizophrenia, cancer, stroke, and a higher risk of developing CVD.
C667T SNP and populations
The existing literature links the prevalence of MTHFR C677T polymorphism to Chinese males to lower eGFR and high blood pressure. In a 2012 report that associated the presence of the C677T SNP in the Chinese population with lower filtration rate and kidney function. Indeed, this study determined that effect was more common in Chinese males when compared to Chinese women.
Additionally, it is essential to note that this SNP prevalence is highly variable within the population. For example, the C677T SNP is less common in the black population (1-2%) when compared to those with European or Australian heritage (8-20%).Â
In heterozygous patients, the enzymatic function of MTHFR can be reduced up to 65%. On the other hand, those patients considered homozygous have a 30% enzyme functionality.
European, North American, and Australian populations have a higher prevalence of having the A1298C mutation. On the other hand, the Asian, Hispanic, and Chinese populations have a lower mutation rate.
However, having two mutations of the MTHFR gene (the A1298C and C677T) results in a combined action, reflecting a decreased enzymatic function and higher tHcy levels.
Does an MTHFR mutation results in health complication?
The main answer is that it depends. A deficient enzymatic function of MTHFR associates with cardiovascular disease, pregnancy complications, neural tube defects, and elevated homocysteine. However, patients with an MTHFR mutation can have normal homocysteine levels. In fact, if the homozygous or heterozygous patient has a constant vitamin B supplementation, this could reduce their risk of developing cardiovascular disease.Â
Furthermore, in multiple countries, folic acid fortified food is the primary prevention factor in reducing the prevalence of pregnancy loss, preeclampsia, clotting disorders, hypertension, and CVD.
Who should get tested for MTHFR mutations?
This question has mixed answers. Kidney failure specialists had become aware of the interaction between genetic mutations and lower eGFR. However, the MTHFR gene mutations have a stronger association with higher homocysteine levels, which can be lowered by folic acid supplementation. This supplementation recommendation is consistent with the KDOQI guidelines specification on vitamins and minerals.Â
On the other hand, in the Chinese male population, the TT genotype directly links with lower eGFR (1.37 ml/min/1.73 m2) than the CC and CT genotypes. On the other hand, the AHA makes evident that there is no indication for mutation testing. However, they consider the recommendations of the American College of Medical Genetics and the American College of Obstetricians and Gynecologists, which state the following:
“Pregnant women should not be tested for MTHFR or homocysteine due to the lack of association between the MTHFR C677T polymorphism and any negative pregnancy outcomes.”
What should we do? Instead, all of the past institutions point back to the importance of supplementing 0.4mg of folic acid to those women of childbearing age. In addition, they are punctual about the fact that MTHFR mutations are not clotting disorders, and they are not predictors of an adverse medical outcome. – Ana Paola RodrÃguez Arciniega, MS.
Dong, Qing et al. “Methylenetetrahydrofolate reductase C677T polymorphism is associated with estimated glomerular filtration rate in hypertensive Chinese males.”Â BMC medical geneticsÂ vol. 13 74. 16 Aug. 2012, doi:10.1186/1471-2350-13-74
Moll, Stephan, and Elizabeth A. Varga. “Homocysteine and MTHFR mutations.”Â CirculationÂ 132.1 (2015): e6-e9.
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Dr. Alex Jimenez DC, MSACP, CCST, IFMCP*, CIFM*, CTG*
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The information herein on "MTHFR Genetic Mutations and its Effects on Health" is not intended to replace a one-on-one relationship with a qualified health care professional or licensed physician and is not medical advice. We encourage you to make healthcare decisions based on your research and partnership with a qualified healthcare professional.
Our information scope is limited to Chiropractic, musculoskeletal, physical medicines, wellness, contributing etiological viscerosomatic disturbances within clinical presentations, associated somatovisceral reflex clinical dynamics, subluxation complexes, sensitive health issues, and/or functional medicine articles, topics, and discussions.
We provide and present clinical collaboration with specialists from various disciplines. Each specialist is governed by their professional scope of practice and their jurisdiction of licensure. We use functional health & wellness protocols to treat and support care for the injuries or disorders of the musculoskeletal system.
Our videos, posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate to and directly or indirectly support our clinical scope of practice.*
Our office has reasonably attempted to provide supportive citations and has identified the relevant research study or studies supporting our posts. We provide copies of supporting research studies available to regulatory boards and the public upon request.
We understand that we cover matters that require an additional explanation of how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez, DC, or contact us at 915-850-0900.
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Dr. Alex Jimenez DC, MSACP, RN* CIFM*, IFMCP*, ATN*, CCST
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