5Department of Public Health, University of Puerto Rico, USA
6Department of Pharmaceutical Sciences, University of Puerto Rico, USA
7Puerto Rico Institute of Statistics, USA
8The Funding Network Puerto Rico, USA
Submission: June 03, 2018;Published:June 27, 2019
*Corresponding author: Raul H Morales Borges, Integrative Optimal Health of Puerto Rico and New Alliance Integrative Research, San Juan, PR Address: 29 Washington St. Suite # 107, San Juan, Puerto Rico, 0907-1509, USA
The methylenetetrahydrofolate reductase (MTHFR) mutation is associated with increased risk of myocardial infarctions, stroke, venous thrombosis, recurrent pregnancy losses between other thrombophilia’s. In our practice we see arterial and venous thromboembolism with no hyperhomocysteinemia, and we see more cases of recurrent pregnancy loses. That is one reason we are proposing this study.
Very high homocysteine levels rarely result from having two common variants alone. People with very high homocysteine levels should be carefully evaluated for other factors known to affect homocysteine. It has been studied high frequencies and prevalence’s in Europeans, Mediterranean’s, and Hispanics, but in general high homocysteine levels associated with these mutations have been related to be thrombogenic, although in our practices we don’t see that.
A cross-sectional assessment of medical records of patients with MTHFR polymorphisms (carriers) within Puerto Rico from multiple physicians’ referrals was made. We reviewed 2752 active records of which 101 cases had the genetic mutation test positive for MTHFR for a prevalence of 3.67% of which only 13.9% had hyperhomocysteinemia although 28.7% had deep venous thrombosis and 12.9% had stroke. We recognized it was a small sample and this is a reason that a larger prospective study is needed.
The methylenetetrahydrofolate reductase (MTHFR) is coded by the gene with the symbol chromosome 1 location p36.3 in humans and there are DNA sequence variants (genetic polymorphisms) associated with this gene, although the two most common ones are C677T and A1298C . MTHFR tells our body how to create an enzyme involved in breaking down the amino acid homocysteine [2-4].
Deficiencies in production or function of this enzyme have been associated with increased risk of myocardial infarctions, stroke, venous thrombosis, several types of cancer congenital defects, inflammatory bowel disease, and several neuropsychiatric conditions.
Studies have found that women with two C677T gene variants have an increased risk for having a child with a neural tube defect . Studies have also found that men and women with two C677T gene variants and elevated homocysteine levels may be at a mild increased risk for blood clots (venous thromboembolism) . In our practice we see arterial and venous thromboembolism with no hyperhomocysteinemia, and we see more cases of recurrent pregnancy loses. That is one reason we are proposing this study.
Very high homocysteine levels rarely result from having two
common variants alone. People with very high homocysteine
levels should be carefully evaluated for other factors known
to affect homocysteine. Doing so may bring to light dietary
deficiencies, thyroid disease, diabetes, high cholesterol, or lifestyle
factors (physical inactivity, smoking and obesity) which can
impact, although it was confirmed that C677T is associated with
high homocysteine levels. If high levels of homocysteine cannot
be explained by these factors, a consultation with a genetics
professional may be helpful in identifying rare genetic causes of
the high homocysteine .
It has been found at high frequencies in Europeans and
American Caucasian population . C677T polymorphism
shows a wide regional and ethnic variation. Homozygosity (TT)
among Whites is 6-14%. In African populations and in Blacks
living outside of Africa such as in Brazil and in the United States,
the frequency falls to less than 2% for the TT variant . The
prevalence rises in Mediterranean and Hispanic population .
For example, among Hispanics in prevalence ranges as high as
21% . As per other reports, in America, about 25% of people
who are Hispanic, and 10-15% of people who are Caucasian have
two copies of C677T .
The A1298C mutation, on the other hand, does not show
as much population variance; its prevalence is more uniform
within the currently studied groups. One study demonstrated
that the high frequencies of the C677T/C677T and C677T/
A1298C diplotypes and haplotypes that are found in Hispanics
may contribute to a wide spectrum of anomalies, especially in
population subject to poor nutrition and low folate intake .
A cross-sectional assessment of medical records of patients
with MTHFR polymorphisms (carriers) within Puerto Rico from
multiple physicians’ referrals was made.
a) Confirm the hypothesis that Puerto Ricans are more
prone than general population in the published medical
literature regarding venous and arterial thromboembolism
with either mutations A1298C or C677T
b) Prove that Puerto Ricans seems that do not need to have
a documented hyperhomocysteinemia to have a thrombotic
We prepared a formulary to collect the data from the medical
records of subjects identified by their physicians collaborating
with the study and a questionnaire for the prospective
ones identified. Once the data was collected a prevalence
estimation (frequency distribution of MTHFR variants and
their corresponding diplotypes/haplotypes) and comparison
of the observed prevalence versus that reported in reference
populations from the 1000 Genome project  (e.g. Puerto
Ricans, Hispanics, Caucasians, African Americans, etc.) in the
study population was performed followed by critical analysis
with articles identified after medical literature reviewed. The
possible barrier we anticipated is the participation of physicians
as volunteers in the study providing their medical records for
review. The study involved human ethics and HIPAA Law due to
patients participating either their medical records or answering
We wanted to determine how important and what clinical
value is to perform the genetic mutations of MTHFR in our
population to identify the ones at risk. To prevent cerebrovascular,
cardiovascular, and obstetric thrombotic events. To teach the
physicians and health professionals to do this test more regularly.
To allow health insurance companies to cover this test. It will be
interesting if more Hispanic population can be included in a near
future such as subjects from Dominican Republic, Virgin Islands,
Central and South America.
There was evidence that we need to do this study in Puerto
Ricans and Hispanics [12-16] and to do comparison with
prevalence studies in humans with other races [8,9,17,18].
We reviewed 2752 active records of which 101 cases had
the genetic mutation test positive for MTHFR for a prevalence of
3.67% (Table 1). Of those cases 81.2% were females and 18.8%
males. Twenty-eight percent of the cases had dyslipidemia, 37.6%
with hypertension, and 18.8% were diabetics. Around 79.2%
were heterozygous and 21% homozygous, 83% were single, and
13.9% had hyperhomocysteinemia. Twenty-one percent of the
cases had anemia, 28.7% with deep venous thrombosis, 12.9%
with stroke, 0.07% with coronary artery disease, 0.04% with
pre-eclampsia, and 0.05% with premature births (Figure 1 & 2)
and (Table 2 & 3).
One study making a relationship with a risk of colorectal
carcinoma (CRC) and MTHFR mutations revealed differences
in the rate of MTHFR gene polymorphism mutations and the
associated risks with CRC across different global populations.
Geographical location played an important role in the rate of
MTHFR gene polymorphisms . This is one reason we need to
do further studies globally to determine the exact expression of
those mutations in different populations.
In our analysis the prevalence was lower than in reported
studies from medical literature. This was a small study sample
and it could be the reason of low prevalence, although a high-risk
population was identified such as patients with Diabetes mellitus
type II, High Blood Pressure, and Dyslipidemia. Interestingly
we identified venous thrombo-embolisms more frequent than
cardiovascular and arterial disease. One fourth of the cases
presented with anemia which can be related to MTHFR mutation.
C677T mutation was higher ten A1298C as described in published
papers before. Our hypothesis regarding hyperhomocysteinemia
was confirmed that Puerto Ricans do not have to express
high homocysteine levels to have thrombotic or ischemic
I agree with Prospective studies of Hispanic women with
these mutations and pregnancy outcomes will establish if there
is a causal relationship
We reviewed 2752 cases of which 101 had the MTHFR mutation for a prevalence of 3.67% of which 13.9% had high homocysteine
levels. Almost one third of the cases have thrombophilia, so, we demonstrated that Puerto Ricans have a higher
prevalence of MTHFR mutations with higher risk of thrombophilia despite having normal homocysteine levels. Larger sample study is recommended.