What are the other names for this Condition? (Also known as/Synonyms)

• ACE I/D Polymorphism
• Angiotensin-Converting Enzyme Insertion-Deletion Polymorphism
• Insertion/Deletion Polymorphism of ACE Gene

What is ACE Insertion/Deletion Polymorphism? (Definition/Background Information)

• The angiotensin converting enzyme gene (ACE gene) located on chromosome 17q23, is responsible for producing the angiotensin-converting enzyme by providing with a set of suitable instructions. The enzyme ACE is made in the walls of the blood vessels; it is present on the surface of epithelial and endothelial cells
• Apart from several other functions, the angiotensin-converting enzyme’s key role is in increasing blood pressure by contracting the blood vessels. It does so by converting the hormone angiotensin I to angiotensin II, an agent that causes constriction of the blood vessel walls. This forms a part of the renin-angiotensin system (RAS) cascade
• Gene polymorphisms (genetic variations or having different forms) are common among human populations; however, for a gene to be considered polymorphic, at least 1% variation must be detected. Many polymorphic variants are “silent”, and they do not affect/alter the gene composition or function
• However, some polymorphisms cause abnormal gene expressions that adversely affect protein production encoded by the specific gene. An abnormal production of protein or an abnormally-formed protein may be associated with diseases or cause to bring about an increased risk for certain medical conditions
• Scientists have identified several significant polymorphisms on the ACE gene. One such widely researched and studied polymorphism is the ACE Insertion/Deletion Polymorphism that is characterized by the presence or absence of a certain sequence denoted as the “287-bp Alu repetitive sequence”
• The presence of certain variations on the ACE gene increases the susceptibility for a variety of conditions such as stroke, kidney complication in diabetes, and certain cancers. The variations to ACE gene occurs when there is an “I” allele (I for insertion) and a variation called the “D” allele (D for missing/deletion of certain portion of the DNA)
• Since individuals have two copies of the ACE gene (one from each parent), one can have the following variations:
  • Two I alleles (called II genotype)
  • Two D alleles (called DD genotype)
  • One I allele and one D allele (called ID genotype)
• Thus, there are three genotypes of ACE I/D Polymorphism that are termed II, DD, and ID. The combination and proportion of these genotypes vary widely from one individual to another, across racial and ethnic communities around the world. According to reports, the insertion/deletion (I/D) polymorphism represents between 20-50% of ACE gene expression variability
• It has been shown that individuals with the DD allele pattern have higher levels of angiotensin-converting enzyme compared to individuals with the II allele pattern genotype. Individuals with the ID allele pattern genotype have intermediate levels of angiotensin-converting enzyme
• Research has further established that the presence of ACE Insertion/Deletion Polymorphism, especially the variant DD allele genotype, serves as an inherent (genetic) risk factor for many conditions that include:
  • Coronary heart disease (CHD)
  • Multiple myeloma (MM)
  • Multiple sclerosis (MS)
  • Myocardial infarction
  • Diabetes associated complications
  • Osteoarthritis
  • Stroke
  • Unstable blood pressure

Who gets ACE Insertion/Deletion Polymorphism? (Age and Sex Distribution)

• ACE Insertion/Deletion Polymorphism is observed in individuals of all age groups and among both male and female genders
• Worldwide, this polymorphism may be present in individuals of all racial and ethnic groups
• However, the frequency of the variants DD, ID and II allele genotypes differs within a given geographical region among the community members

What are the Risk Factors for ACE Insertion/Deletion Polymorphism? (Predisposing Factors)

• Presently, there are no clearly identified risk factors for ACE Insertion/Deletion Polymorphism
• Certain members of a race or ethnic group may show a higher prevalence for specific genotype variants (either of the DD, ID, or II allele genotypes)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of ACE Insertion/Deletion Polymorphism? (Etiology)

The cause of ACE Insertion/Deletion Polymorphism is unknown.

• However, it occurs due to certain genetic variations during fertilization between the sperm and ovum
• Across the world, different racial and ethnic groups are reported to show different incidences of II, ID, and DD genotypes

What are the Signs and Symptoms of ACE Insertion/Deletion Polymorphism?

• There are no observable “direct” signs and symptoms associated with ACE Insertion/Deletion Polymorphism
• One suspects the presence of ACE I/D Polymorphism depending on certain conditions, such as high blood pressure that is difficult to control, or the development of kidney complications in diabetes

How is ACE Insertion/Deletion Polymorphism Diagnosed?

• The presence of ACE Insertion/Deletion Polymorphism is detected through gene sequencing of the ACE gene
• This gene sequencing can be performed on a blood test in specialized molecular laboratories

If the healthcare provider suspects that there is an increased for a medical condition due to a genetic risk factor, he/she may undertake certain evaluations to assess the same. Such tests and exams may include:

• Complete physical evaluation
• An assessment of signs and symptoms, if any present
• Comprehensive analysis of family medical history
• Imaging tests, if necessary
• Biopsy studies

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of ACE Insertion/Deletion Polymorphism?

Individuals with ACE Insertion/Deletion Polymorphism, particularly those with the variant DD allele genotype, have an increased risk for certain conditions and complications such as:

• Cardiovascular diseases such as heart attack, coronary heart disease, and increased/decreased blood pressure
• Brain stroke
• Diabetic nephropathy, from types I and II diabetes
• Gestational diabetes mellitus (GDM)
• Multiple myeloma
• Multiple sclerosis
• Osteoarthritis
• Peripartum cardiomyopathy
• Certain cancers

How is ACE Insertion/Deletion Polymorphism Treated?

• The presence of the variants DD, ID, or II genotypes increases one’s susceptibility of developing certain associated complications in diabetes. Thus, it is important to take this information while planning treatment for the same
• In diabetics with documented variant DD allele genotype, monitoring of kidney function should be performed on a regular basis. This will help manage diabetic nephropathy better through early recognition
• Similarly, in individuals with variant DD allele genotype having hypertension, it is important to aggressively manage blood pressure to reduce the chances of a brain stroke

In general, the healthcare provider may assess treatment requirements based on the conditions that develop in an individual. However, an awareness of ACE Insertion/Deletion Polymorphism may aid in appropriate disease management decisions.

How can ACE Insertion/Deletion Polymorphism be Prevented?

• Currently, ACE Insertion/Deletion Polymorphism is not preventable, since it is a genetic event
• Active research is currently being performed to explore the susceptibility of individuals with the variants DD, ID, or II genotypes to certain medical conditions

In case of an increased risk for certain medical conditions, regular medical screening at periodic intervals with tests and physical examinations may be planned and/or recommended.

What is the Prognosis of ACE Insertion/Deletion Polymorphism? (Outcomes/Resolutions)

• The overall prognosis of individuals with ACE Insertion/Deletion Polymorphism depends on the nature and severity of the underlying condition, if any present
• An increased risk for a specific condition may call forth for increased vigilance and periodic visits to one’s primary care provider, as necessitated
• In general, the variant DD allele genotype shows a higher susceptibility compared to the variants DI and II allele genotypes of the ACE gene

It is important to note that even though according to current evidence based on research, ACE I/D Polymorphism is implicated in the development of several cancers (including breast cancer, lung cancer, oral cancer, prostate cancer, and stomach cancer), some researchers have challenged this hypothesis and questioned the direct link between the two.

Additions and Relevant Useful Information for ACE Insertion/Deletion Polymorphism:

• It is observed that athletes who utilize short bursts of energy, such as sprint runners and short distance swimmers, are found to have to a higher frequency of the variant DD genotype
• While, athletes who utilize sustained energy levels over prolonged periods, such as marathon runners and long-distance swimmers, are found to have higher frequency of the variant II genotype

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/