I am a Physician
specializing in Endocrinology, which is a specialty which has always been
micro-molecular in its outlook and depth. As science evolves, the endocrine
metabolism is usually in the forefront of benefit from these scientific
discoveries as we, endocrinologists are eager to put these scientific breakthroughs.
SNP or Single Nucleotide
Polymorphisms has been one such thing of the Genomic studies of the humans.
They find that the misreading of the genetic code either confers or increases
the chances of particular changes in the functions at the molecular levels.
From the NET:
Single nucleotide polymorphisms,
frequently called SNPs (pronounced “snips”), are the most common type of
genetic variation among people. Each SNP represents a difference in a single
DNA building block, called a nucleotide. For example, a SNP may replace the
nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of
DNA.
SNPs
occur normally throughout a person’s DNA. They occur almost once in every 1,000
nucleotides on average, which means there are roughly 4 to 5 million SNPs in a
person's genome. These variations may be unique or occur in many individuals;
scientists have found more than 100 million SNPs in populations around the
world. Most commonly, these variations are found in the DNA between genes. They
can act as biological markers, helping scientists locate genes that are associated
with disease. When SNPs occur within a gene or in a regulatory region near a
gene, they may play a more direct role in disease by affecting the gene’s
function.
Most
SNPs have no effect on health or development. Some of these genetic
differences, however, have proven to be very important in the study of human
health. Researchers have found SNPs that may help predict an individual’s
response to certain drugs, susceptibility to environmental factors such as
toxins, and risk of developing particular diseases. SNPs can also be used to
track the inheritance of disease genes within families. Future studies will
work to identify SNPs associated with complex diseases such as heart disease,
diabetes, and cancer.
I have always had
the good fortune of working with excellent colleagues during my days with
various Indian tribes in the USA, they all have been helpful in stimulating my
mind and being receptive to my ideas which may have sounded bizarre to other
doctors. As Michele Smith of the Omaha/Winnebago put it: You are just a few
years ahead of others. I thank Coleen Peerman, Lyn Lawry, Dar Buena Suerte
Goodman, Ashleen Blackbird just to name a few.
Lately I am with two
excellent colleagues, Susan Dethman a doctoral level Nutritionist and Anna v, a
diabetes educator plus a fitness specialist and an open-minded guide to the
health of the Native people under her care. Our discussions have led to
wonderful results for our patients. The technology has been very helpful too.
In a family unit,
composed of four adults suffering from the chronic diseases of the time
Diabetes
Hypertension
Hypercholesterolemia
Fatty Liver
They instituted a
regime of:
Consulting them
before a meal is prepared and provided to the patient
Thus, the two
colleagues were able to influence the eating habits and cooking habits of the
family unit. The helper/cook assigned to the family would send pictures of the
food prepared before and after and received helpful hints in return. They were
instructed to buy Organic food whenever possible.
Whilst they were
under the care of a Family Practitioner, an Endocrinologist and a Cardiologist,
within six weeks of this social experiment resulted in changes that surprised
all three of the health care providers.
Without any changes
in medications
There was a decrease
in
Hemoglobin A1c.
meaning improvement in glucose metabolism
BP readings were heading
down, meaning good protection of the heart and the kidneys
Cholesterol values
were coming down both the bad cholesterol and the Triglycerides, showing a
decrease in inflammation as well as protection of the heart.
Welcomingly enough
the evidence of a fatty liver completely disappeared, as shown by the blood
tests.
On their next visit
to their doctors, they had to request decrease in medications for their
particular conditions.
This is a social adjustment
rather than a medical experiment and from this we could surmise that the people
had become receptive to the changes and that perhaps SNPs were involved, even
though we do not know what they are.
So, it was
heartwarming to read about the SNP changes in Fatty liver that are directly involved
in inflammation that causes cardiovascular diseases
Non-alcoholic fatty
liver disease (NAFLD) is highly prevalent among individuals with type 2
diabetes. Although epidemiological studies have shown that NAFLD is associated
with cardiovascular disease (CVD), it remains unknown whether NAFLD is an
active contributor or an innocent bystander. Plasma lipids, low-grade
inflammation, impaired fibrinolysis and hepatokines are potential mediators of
the relationship between NAFLD and CVD. The Mendelian randomization approach
can help to make causal inferences. Studies that used common variants in
PNPLA3, TM6SF2 and GCKR as instruments to investigate the relationship between
NAFLD and coronary artery disease (CAD) have reported contrasting results.
Variants in PNPLA3 and TM6SF2 were found to protect against CAD, whereas
variants in GCKR were positively associated with CAD. Since all three genes
have been associated with non-alcoholic steatohepatitis, the second stage of
NAFLD, the question of whether low-grade inflammation is an important mediator
of the relationship between NAFLD and CAD arises. In contrast, the differential
effects of these genes on plasma lipids (i.e. lipid-lowering for PNPLA3 and
TM6SF2, and lipid-raising for GCKR) strongly suggest that plasma lipids account
for their differential effects on CAD risk. This concept has recently been
confirmed in an extended set of 12 NAFLD susceptibility genes. From these
studies it appears that plasma lipids are an important mediator between NAFLD
and CVD risk. These findings have important clinical implications, particularly
for the design of anti-NAFLD drugs that also affect lipid metabolism
2020
Genome-wide association studies (GWAS) in the field
of liver diseases have revealed previously unknown pathogenic loci and
generated new biological hypotheses. In 2008, a GWAS performed in a
population-based sample study, where hepatic liver fat content was measured by
magnetic spectroscopy, showed a strong association between a variant (rs738409
C>G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3)
gene and nonalcoholic fatty liver disease. Further replication studies have
shown robust associations between PNPLA3 and steatosis, fibrosis/cirrhosis, and
hepatocellular carcinoma on a background of metabolic, alcoholic, and viral
insults. The PNPLA3 protein has lipase activity towards triglycerides in
hepatocytes and retinyl esters in hepatic stellate cells. The I148M
substitution leads to a loss of function promoting triglyceride accumulation in
hepatocytes.
2016
Exciting times lay ahead for us who are
interested in these scientific developments.
Within the next year, the patients under the
care of the three of us, would receive as a preliminary determination of their
status:
Microbiome, determined by the Israeli
scientists Eran Segal and Eran Elianav, now available in the USA
A relevant determination of SNPs, to see
their absence or presence
Appropriate Nutrigenomic advice in which we
can use Nutrition to take advantage of the Microbiome as well as the
presence/absence of SNPs.
Exciting times to be looking after people, in
our case, the indigenous peoples of this planet.
