Unless someone swipes one of President Trump’s used forks from the Mar-a-Lago dining room and sends it to 23andMe for DNA analysis, the world will simply have to guess what the White House physician meant when he told reporters on Tuesday that Trump “has incredible genes, I just assume.”
“Incredible genes” may seem like hand-waving, but there’s no question some genetic variants protect against heart disease, hypertension, diabetes, and other killers. And Trump chose his parents well: His father died of pneumonia at 93 after developing Alzheimer’s disease but apparently avoiding cancer and heart disease. His mother lived to 88; her cause of death was not reported, but her only known ailment was osteoporosis.
His genetic inheritance might explain how Trump can get by with only four or five hours of sleep, which supposedly raises the risk of hypertension, and yet have blood pressure of 122/74 without anti-hypertensive medication. (At 71, Trump is in the age group for which the systolic target, the first number, is 130.)
His genes also might explain how he can consume a high-fat, low-fruit-and-vegetable diet, which is linked to heart disease, and yet have what his physician, Rear Admiral Ronny Jackson, called “excellent” cardiac health. (Trump takes a statin, Crestor, to lower his blood cholesterol, and although there has been a lot of internet chatter about his coronary calcium reading of 133 being unhealthy, it is better than more than half of men his age.)
His luck might not last, however. “Even if Trump has been dealt a good genetic hand, he’s certainly not helping himself” with an unhealthy lifestyle, said Dr. Sekar Kathiresan, a cardiologist and geneticist at Massachusetts General Hospital and the Broad Institute who has done seminal work in protective DNA variants. People whose genes lower their risk of disease “can mess that up.”
The first generation of gene-disease studies, which focused on unusual families, discovered DNA variants that increase the risk of some disorder. “Families with a decreased risk of cardiovascular disease or cancer wouldn’t even come to scientists’ attention,” said Dr. Chris Newton-Cheh, a genetics researcher at Mass. General whose lab studies genes that reduce the risk of hypertension. But starting in about 2005, using an approach called genome-wide association studies (GWAS), protective variants starting popping up all over, he said.
Most studies of how genes and lifestyle interact focus on how people with a high genetic predisposition to a disease can reduce their risk by following healthy habits. A 2015 study, for instance, found that if people with a high genetic risk for coronary artery disease have at least three of four healthy habits (not smoking, exercising once a week, healthy weight, and healthy diet), they can cut that risk by nearly half.
Fewer studies look at the opposite — genetic variants that reduce people’s risk of disease despite a lifestyle that raises that risk — because scientists have been wary of giving people a get-out-of-jail-free card, Newton-Cheh said. But such research has picked up with the realization that such protective genes might be exploited for drug discovery: Figure out what the gene does, and you might be able to mimic it with a drug.
Mutations in at least three genes reduce systolic blood pressure, scientists at Yale University discovered. The genes are involved in how the kidneys handle salt, perhaps explaining how some people who eat a high-sodium diet manage to avoid hypertension. Carrying one of the 30 identified mutations was associated with systolic blood pressure 6.3 points lower, on average, than in people without the protective mutations. And the protective effect increased with age, Dr. Richard Lifton of Yale and his colleagues found: Systolic blood pressure in these winners of the DNA lottery was 5.7 points lower at age 40 and 11.5 points lower in people older than 60.
Lifton estimated that 100 million people worldwide have the hypertension-protective mutations. Since they were discovered in the Framingham Heart Study, whose largely Caucasian participants share Trump’s genetic ancestry, his chance of having one or more of the them is higher than average.
Scores of DNA variants protect against heart disease, as well as high triglycerides and high levels of “bad” cholesterol, which are considered risk factors for heart disease. In one famous example, scientists discovered that rare mutations in the PCSK9 gene on chromosome 1 knock down levels of bad (low-density lipoprotein, or LDL) cholesterol to astonishingly low levels. The discovery led to new drugs that inhibit normal PCSK9, including Amgen’s evolocumab (Repatha), though their high price has limited their use.
Maybe Trump is one of the 1 in 650 people who carry a mutation in their NPC1L1 gene, which reduces LDL cholesterol and cuts the risk of coronary heart disease by about half. As it happens, this is the gene that Merck’s ezetimibe (sold as Zetia) targets, but the drug was developed before the genetic variant was discovered.
At least four rare mutations both lower levels of triglycerides and, probably as a consequence, reduce the risk of coronary heart disease 40 percent. The mutations disable the gene APOC3, Kathiresan and colleagues discovered. Since APOC3 makes a protein that prevents the removal of fats from the blood, disabling the gene releases the brakes on that removal. Result: Mutation carriers have triglyceride levels of about 85, compared with the population average of 150 or so.
Trump’s triglycerides clocked in at 129, high enough that Jackson wants him to exercise and start eating healthier meals. If the president has one of the protective mutations, it might explain why his Big-Mac-heavy diet hasn’t raised his triglycerides even further. These mutations were first discovered in the Amish, but have now been found in people of other European ancestry, too. Trump’s roots are Scottish and, like the Amish, German.
The Global Lipids Genetics Consortium has identified 46 genes involved in HDL (“good”) cholesterol, nine with LDL cholesterol, and 16 with triglycerides. More intriguing, however, are that 30 of the 45 genes most strongly associated with heart attacks and coronary artery disease don’t affect cholesterol or other risk factors.
Reporters at the White House briefing on Tuesday seemed especially incredulous that Trump has apparently not reaped what his diet and sedentary habits sowed: type 2 diabetes. He weighs 239 pounds, putting him within one pound of being obese for his 6-foot-3-inch height, and obesity is a leading risk factor for type 2 diabetes. Yet Trump’s fasting blood glucose, a measure of whether his cells are responding to insulin and absorbing sugar from the blood, is 89. (Anything under 100 is good.)
At least one DNA variant, in the gene called WRN, protects against type 2 diabetes, or at least delays its onset. But about one-third of obese people escape diabetes. Only one-third of overweight people develop diabetes, so even without “incredible” genes, Trump has a 2-in-3 chance of escaping that disease. Sometimes being lucky can trump living unhealthily.
But not necessarily forever. “If you have protective genetic factors but adopt unhealthy lifestyle habits, it will weaken the genetic benefits you were born with,” Newton-Cheh said. “You can still do yourself in.”
How badly? People with a high genetic risk for atherosclerosis but a healthy lifestyle had a 5.1 percent risk of suffering a heart attack over a 10-year period, Kathiresan said. People with a low genetic risk, perhaps like Trump, and an unhealthy lifestyle had a 5.8 percent risk.