How genes affect response to medication. Asthma. Plavix. 1

Plavix is useless in 65% of people with Asian DNA ancestry. We know that different racial groups have different risk profiles for disease. We also know that different racial groups respond to treatment in different ways. We demonstrated that patients with the highest prevalence of asthma have the lowest medication response to asthma medications. 

Precision medicine is already here. Dr. Anton Titov, MD. It is 4P Medicine: Predictive, Personalized, Preventive and Participatory. Individual genetic DNA ancestry influences response to medications. Take example of blood-thinning medication Plavix (clopidogrel). Dr. Esteban G. Gonzalez, MD. This medication is useless in 65% of Asians. Because they have genetic mutation that renders drug useless. How genes affect response to medication. Examples of individual variability in response to asthma treatment and Plavix (clopidogrel). Hispanic ethnicity can mean poor response to asthma treatment. Top Genetics and Precision Medicine expert explains. Precision medicine helps individual patients to get the treatment that works best for them. Interview with Medical Second Opinion, genomics expert. The goal is to develop targeted treatments for each person. Video interview with top expert in medical genetics and asthma. Medical second opinion confirms that asthma diagnosis is correct and complete. Dr. Anton Titov, MD. Medical second opinion ensures that genetic DNA ancestry information is included in diagnosis of asthma. Medical second opinion also helps to choose the best personalized treatment strategy for asthma in children and adults. Seek medical second opinion on asthma and be confident that your precision medicine treatment is the best. How my genes affect response to medicines. Dr. Esteban G. Gonzalez, MD. Personalized medicine. precision medicine. Medical Second Opinion. “4P Medicine”: Predictive, Personalized, Preventive and Participatory. Dr. Anton Titov, MD. This term defines in a very ambitious goal in precision medicine. We know that pharmaceutical companies pursue blockbuster medicines. Pharmaceutical companies market medicines to millions of people around the world. There is no regard for person’s unique genetic makeup. You use genetics to determine individual response to medications. This is a forefront of precision medicine. You work to determine serious side effects from medications. Your do research is asthma in children. Asthma should not be a fatal disease in modern society. Unfortunately, asthma sometimes still leads to death of children. Personalized medicine can help treat asthma better. What does your research show about the interaction between genetic and environmental factors? Dr. Anton Titov, MD. How individual response to medications is determined? How can you predict the probability that a person will experience side effects from any medication? Medical Second Opinion. Professor of Pharmacogenomics, UCSF. Dr. Esteban G. Gonzalez, MD. We know that different racial groups have different risk profiles for disease. We also know that different racial groups respond to treatment in different ways. We demonstrated that patients with the highest prevalence of asthma have the lowest medication response to asthma medications. Patients with highest death rates from asthma respond to medications poorly. These medications are used all over the world to treat asthma. Precision medicine can help to improve asthma treatment. Other scientists studied blockbuster medicines, for example, Plavix or clopidogrel. Plavix is used to treat heart attacks or strokes. Scientists found that you need an enzyme cytochrome P450 to make an active form of Plavix. This active form of clopidogrel creates therapeutic effects. A special mutation has to be present in the enzyme to convert Plavix into active form. 65% of Asians do not have this mutation. Therefore 65% of Asian people cannot convert inactive prodrug into active form of Plavix. Only active form of Plavix has therapeutic effect. So we are giving a placebo to many Asians. They have a heart disease or stroke. Placebo is a substance without any objective treatment effect. The interesting part is that. Pharmaceutical companies that make Plavix (clopidogrel) for the last 10 years know about this problem with Asians. These pharmaceutical companies are Bristol Myers Squibb and Sanofi Aventis. But they continue to market clopidogrel (Plavix) to millions of people around the world. Because Plavix is very profitable for them. It is a multi-billion dollar medication. The Attorney General of Hawaii recently filed a lawsuit against these pharmaceutical companies. He sued them on behalf of people of Hawaii. Because pharmaceutical companies marketed medication that does not work. These pharmaceutical companies knew about this fact. They have known it for 10 years. Dr. Esteban G. Gonzalez, MD. Plavix does not work for 65% of Asians. Therefore pharmaceutical companies showed “willful deceit” and negligence. This is an example how genetic DNA ancestry at a particular gene influences risk of disease. Plavix genetic DNA ancestry determines poor response to medication. There are hundreds of cases in this. The FDA (Food Drug Administration of the United States) has included in the medication package insert information about importance of genetic DNA ancestry for treatment efficacy and side effects. This information talks about importance of genetic DNA ancestry on global level and also on individual gene level. This is example of benefits of precision medicine for each person. We are conducting genetic research on asthma. We have built the largest pediatric asthma genetic clinical trial in the United States. It is also the most racially diverse clinical trial of genetic influences in asthma in the United States and in the world. We are looking at the extremes in the prevalence in death rates. We are asking the question. Are there genetic variants that predict the response of the child to asthma treatment medication? Which child is going to have a good response to asthma medication? Dr. Anton Titov, MD. Which child is going to have a bad response to treatment of asthma? This is application of precision medicine to asthma. Dr. Esteban G. Gonzalez, MD. We would like to be able to say. “Dear patient, you have this particular mutation. These medications will work well for you. Those medications will not work well for you. This is a goal of precision medicine. Race or ethnicity should not matter for treatment response. Dr. Titov’s note. Genetic DNA ancestry matters most at individual gene level. It matters less in a broad racial group. This is a goal of precision medicine. Dr. Anton Titov, MD. How genes affect response to medication. Precision medicine examples of Asthma in children and Plavix. Interview with Professor Esteban G. Burchard MD (UCSF)