"Genetic Health does more than hit just a home run it's a grand slam in the bottom of the ninth to win the game ... one of the very best health-related sites we have ever had the pleasure to view." Wally Gross, Surfers Choice Review Team
"This coveted award is only given to sites which excel not only in user-friendly design but also in depth of content. Your site has exceeded all of our expectations in these areas. We were particularly impressed by the amount of detailed and useful information that you make available to your visitors." Eye-Dentity Web Team
| Genes Can Cause Coronary
Friedrich, MD, PhD and Andy
is no question that coronary artery disease (CAD) runs
in families. We know that first-degree relatives
of people who develop CAD at an early age are at a much
higher risk for developing CAD than the general population.
By better understanding the genetics of this disease,
you can more accurately assess your risk and be on the
lookout for early warning signs.
have identified more than 250 genes
that may play a role in CAD. Although researchers are
a long way from confirming whether even half of those
genes are actually involved, we do know that CAD often
results from the blended effects of multiple genes.
These so-called polygenic effects mean that the genetics
of CAD are extremely complicated, with many different
genes influencing a person's risk. In most cases, CAD
is not inherited in a clearly dominant
manner. Instead, a person may have mutations
in some genes that increase risk and mutations in other
genes that decrease risk. On average, a person's risk
level is approximately midway between those of the parents.
than discuss all 250 genes that have been implicated,
it makes sense to focus on several of the best-understood
genes. As you examine the following information, keep
in mind that this field is rapidly changing. The roles
of many of these genes have not yet been fully defined.
recent news about genes that are implicated in CAD,
see Related News below.
genes linked to CAD are involved in how the body removes
low density lipoprotein (LDL) cholesterol from the bloodstream.
If LDL is not properly removed, it accumulates in the
and can lead to CAD.
The protein that removes LDL from the bloodstream
is called the LDL receptor (LDLR). In 1985, Michael
Brown and Joseph Goldstein were awarded a Nobel prize
for determining that a mutation in this gene was responsible
for familial hypercholesterolemia, or FH. People with
FH have abnormally high blood levels of LDL. In FH,
one or both of the LDLR genes has a mutation that
makes the receptor inactive or inefficient. One in
500 people have a mutation in at least one of their
some diseases, where one specific mutation is responsible
for the disease, many different mutations in the LDLR
gene can lead to FH. In some people with this disorder,
the receptor is simply not produced. In others, it
binds LDL poorly or not at all. In the most severe
cases, people with FH may actually have heart attacks
is inherited in a dominant manner. This means that
you only have to inherit a defective LDLR allele from
one parent in order to be at a very high risk for
developing CAD. Even in people who have just one defective
gene, the consequences are dramatic: LDL cholesterol
levels are twice normal by the age of two, and CAD
appears by age 30 to 60 in men and 50 to 80 in women.
(For news about detecting people with familial hypercholesterolemia,
see Related News below.)
As with LDLR, mutations in the apo E gene affect blood
levels of LDL. More than 30 mutant forms of apo E
have been identified. Interestingly, not all of these
mutations are bad. People carrying the e4 version
of the gene tend to have higher cholesterol levels
than the general population, but levels in people
with the e2 version are significantly lower. The apo
E gene has also been implicated in Alzheimer's disease.
Apo B-100 is a component of LDL. Mutations of this
gene result in LDL staying in the blood for longer
than normal, leading to very high LDL levels. In people
of Western European descent, one person in 500 has
a mutation in the Apo B-100 gene. A mutation called
ApoB3500 is the most common mutation found in people
with a disease called familial defective apolipoprotein
is a glycoprotein that combines with LDL to form a
particle called Lp(a). Lp(a) is often found as a part
of plaques on blood vessels.
People with high Lp(a) levels (over 30 mg/dL) in their
blood have a higher risk of developing CAD. The actual
structure of Lp(a) varies greatly from person to person,
so the genetics of mutations in the apo(a) gene are
not well understood. Lp(a) levels are not part of
routine lipid panels and must be specifically ordered.
If you have a relative with high Lp(a) levels, be
sure to ask your doctor to measure your own levels.
Lp(a) levels may be reduced by treatment with niacin,
or by hormone replacement therapy in postmenopausal
blood levels of homocysteine (a condition called hyperhomocystinemia)
is known to be a risk factor for CAD. In almost all
human tissues, normal cellular processes generate a
waste product called homocysteine. Homocysteine is then
cleared from the blood and recycled.
MTHFR is one of the enzymes
that clears homocysteine from the blood. In the US,
about one in eight people have a mutation in the gene
that makes MTHFR, which results in mild elevations
in blood homocysteine. People with mutations in both
of their MTHFR genes may have slightly higher homocysteine
levels. Doctors treat hyperhomocystinemia with folate
Cystathione B-synthase, or CBS,
is another enzyme involved in homocysteine metabolism.
People who have mutations in both alleles of the CBS
gene have a condition called homocystinuria, in which
blood levels of homocysteine are so high that it can
be detected in the urine. Homocystinuria is usually
diagnosed in childhood; it typically causes mental
retardation as well as heart disease.
enzyme called angiotensin Converting Enzyme (ACE) helps
the body regulate blood pressure by causing blood vessels
to constrict. Even though ACE has been studied extensively,
many of the investigators have reported conflicting
results. Several studies have implicated a particular
mutation (called the ACE (I/D) polymorphism) in CAD.
However, these studies involved small numbers of people
and have yet to be repeated with larger groups.
is a protein that is packaged along with cholesterol
in high density lipoprotein (HDL, the "good cholesterol").
Certain mutations in the apo A1 gene result in low
apo A1 levels, low HDL levels, early heart attacks,
and strokes. In general, overall HDL levels are a
good indication of Apo A1 levels; Apo A1 is not usually
Scientists are especially interested in one particular
mutation in Apo A1 found in some residents of Milan,
Italy. The "Milano" mutation results in very low levels
of HDL; however, this mutant HDL is exceptionally
efficient at removing plaque from arteries. Thus,
although these people have very low levels of HDL,
they also have a low incidence of CAD. Pharmaceutical
companies are currently trying to develop a compound
that will mimic this genetic effect.
IIb/IIIa is a protein that is present on the outer
surface of certain blood components that play a critical
role in blood clotting. A recent study found that
this gene was mutated in half of patients under age
60 who were admitted to a hospital intensive care
unit with CAD. Since heart attacks often result from
the formation of blood clots, this is an interesting
candidate gene for heart disease. New treatments that
focus on glycoprotein IIb/IIIa are now available for
heart attack patients.
general, tests for specific genetic mutations are not
performed in CAD. There are several reasons for this.
First, it is not clear how much additional information
this kind of information provides beyond the usual methods
for assessing cardiac risk. Second, the best way you
can avoid CAD is to modify your lifestyle to reduce
environmental risk factors. This is especially true
if you have a strong family history of CAD. While this
subject is still under study, it is likely that people
with a strong family history may be more susceptible
to the effects of risk factors. If you have a strong
family history of CAD, your main course of action is
to vigorously reduce risk factors that you can control,
such as smoking, blood pressure, diabetes, obesity,
and cholesterol levels.
some genes, indirect tests can be used to determine
if there is a mutation. For example, it is much easier
and less expensive to measure blood levels of homocysteine
than it is to perform genetic testing. Most people with
mild elevations of homocysteine respond well to treatment
with folate supplements. If a person fails to respond
to folate treatment, other causes of elevated homocysteine,
such as vitamin B12 or vitamin B6 deficiency, should
be tested. Cholesterol levels are another example. Regardless
of the specific genetic cause of elevated cholesterol,
the approach to testing and treatment is the same.
M. (2000) Epidemiology and prevention of coronary heart
disease in families. American Journal of Medicine,
Brown, M.S., et al. (1981) Regulation of plasma cholesterol
by lipoprotein receptors. Science, 212, 628-635.
Rosenblatt, D.S. (1995) Inherited disorders of folate
transport and metabolism. In C.R. Scriver et al. (Eds.),
The Metabolic and Molecular Bases of Inherited Disease
(pp.3111-3128). New York, NY: McGraw-Hill Book Co.
Ellsworth, D. L., et al. (1999) Coronary heart disease:
at the interface of molecular genetics and preventive
medicine. Am J Prev Med, 15(2), 122-133.
©Copyright 2011 Latest Medical, Inc.. All Rights Reserved.