Developing precision medicine for people of East Asian descent
© The Author(s). 2016
Received: 23 September 2016
Accepted: 4 November 2016
Published: 11 November 2016
The goal of precision medicine is to separate patient populations into groups to ultimately provide customized care tailored to patients. In terms of precision medicine, ~540 million people in the world have a genetic variant of the aldehyde dehydrogenase 2 (ALDH2) enzyme causing a flushing response and tachycardia after alcohol consumption. The genetic variant is identified as ALDH2*2 and originates from East Asian descendants of the Han Chinese. The variant is particularly important to consider when discussing lifestyle choices with patients in terms of risk for developing specific diseases, preventative screening, and selection of medications for treatment. Here we provide examples why patients with an ALDH2*2 variant need more individualized medical management which is becoming a more standard practice in the precision medicine era.
In 2015, the National Institutes of Health launched the precision medicine initiative. This initiative describes precision medicine as “an emerging approach for disease prevention and treatment taking into account people’s individual variations in genes, environment, and lifestyle” with the ultimate goal of implementing these concepts into clinical practice .
Some examples of precision medicine already exist in medical practice. For example in pediatrics, a genetic panel is typically used when a child is born, known as a newborn screen, which in California tests for 57 different conditions. If one of these genetic conditions is identified from the screen, individualized and rather specific care is provided which can prevent serious health problems. Another example is recommendations for disease surveillance based upon single gene variants which increase the risk for colon cancer as seen in individuals with Lynch syndrome or familial adenomatous polyposis. These patients have established personalized guidelines relevant to the frequency of medical surveillance for colon cancer by colonoscopy which differs from colon cancer screening measures recommended to the general population .
Physicians are now also considering the influence of genetic variants on drugs they prescribe when treating specific conditions. For example, a variant in P450 CYP2C19 reduces the amount of the active form of clopidogrel (a drug given when treating atrial fibrillation). This is concerning since a subset of people with atrial fibrillation and the CYP2C19 variant may not achieve a therapeutic level of clopidogrel if prescribed the medication. Recently, physicians have started implementing screening for the CYP2C19 variant as part of the medical decision making process when determining which drug to prescribe for atrial fibrillation .
Similar to the examples above, here we describe a genetic variant which when factored in with environment and lifestyle choices will influence medical management, preventative medicine, and drug treatment choices. This genetic variant of the aldehyde dehydrogenase 2 (ALDH2) enzyme is present in ~8 % of the world's population. Here, we also briefly outline the initial steps for implementing precision medicine in the clinic for patients with this variant.
Developing precision medicine for ALDH2*2 in relation to cancer risk
Undoubtedly, lifestyle choices contribute to the risk of developing cancer. In particular, alcohol consumption and cigarette smoking are two lifestyle choices which increase the risk for esophageal cancer. Cigarettes contain several reactive aldehydes (such as acrolein, formaldehyde and acetaldehyde) which are known carcinogens . The acetaldehyde produced from breaking down alcohol also is metabolized to acetaldehyde by the ALDH2 enzyme.
Taking this risk into consideration, similar to published outlined measures for gastrointestinal cancers with reference to specific genetic variants , increased consideration should be given to developing screening measures for esophageal cancer in the ALDH2*2 population. This could potentially reduce the incidence of esophageal cancer within the East Asian population. Further, screening for the ALDH2*2 gene could be used as topic of conversation with patients as a preventative measure to reduce esophageal cancer risk. These discussions could include how the ALDH2*2 variant in combination with lifestyle choices such as drinking alcohol or smoking cigarettes increases the relative risk of developing esophageal cancer. Together, effectively communicating these lifestyle risks can be a powerful means to reduce esophageal cancer incidence.
Integrating the ALDH2*2 variant into medical decisions when prescribing drugs
Importantly, the influence of ALDH2*2 on nitroglycerin metabolism may impact medical decision making in several medical disciplines including anesthesiology, obstetrics, cardiology, internal medicine, and emergency medicine. Nitroglycerin is commonly given after cardiac bypass for a heart valve replacement or coronary artery bypass grafting. Nitroglycerin is also used in obstetrics to relax the uterus. In cardiology and emergency medicine, nitroglycerin is frequently given to relieve chest pain associated with myocardial ischemia. Many of these nitroglycerin applications in medical practice may need to consider potential ALDH2*2 variant effects on nitroglycerin efficacy. With knowledge of this genetic information, clinicians can consider either increasing the nitroglycerin dose given or choosing another vasodilator which is not metabolized by the ALDH2 enzyme, such as nitroprusside.
With a focus on precision medicine and the high prevalence of the ALDH2*2 variant within the East Asian population, clinicians should consider whether a patient has this variant which increases the risk for specific diseases such as esophageal cancer and limits the metabolism of specific drugs such as nitroglycerin. One option to consider is more frequent screening for esophageal cancer for those with both the ALDH2*2 variant and a history of smoking cigarettes and/or consuming alcohol. When the potential influence of the ALDH2*2 variant is taken into consideration, relative to disease risk and drug metabolism, patients with the ALDH2*2 variant can begin receiving personalized medical management which will become standard practice in the precision medicine era.
Supported by the National Institutes of Health, National Institute of General Medicine (GM119522 and GM089626).
Availability of data and materials
KS and SM assisted with drafting and editing the manuscript in addition to contributing to manuscript design. EG wrote the manuscript. All authors read and approved the final manuscript.
EG, an Anesthesiologist and basic scientist, is developing a precision medicine platform for those of East Asian descent.
The authors declare that they have no competing interests.
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