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Researchers Making Progress On Causes of Vitiligo

Close up fashion portrait of a african male with white pigmentation caused by vitiligo.

AURORA, Colo. (July 30, 2019) – A pair of new journal articles by researchers at the University of Colorado School of Medicine indicate that both genetic and environmental factors play significant roles in the onset of vitiligo, an autoimmune disease that results in the loss of color in blotches of skin.

The findings also show that while the tools for scientific understanding of the genetic basis of a complex disease like vitiligo have advanced, there are still many other as-yet-unidentified factors that contribute to vitiligo’s onset.

“Vitiligo has been perhaps the easiest of all complex diseases to sort out,” said senior author Richard A. Spritz, MD, director of the Human Medical Genetics Program and professor of pediatrics at the CU School of Medicine. “Through years of previous studies, we have identified what could be called a ‘vitiligo parts list’ of 50 common contributory genes/risk variants.”

Spritz and his co-authors reviewed two types of vitiligo cases – simplex and multiplex. In most instances, vitiligo appears in individuals with no family history of the disease, which are referred to as the simplex cases. In the multiplex cases, there are other family members with vitiligo.

A paper by Spritz and his co-authors in The American Journal of Human Genetics combines the 50 vitiligo common risk variants together to make a vitiligo “genetic risk score,” and then compared the simplex and multiplex cases.

“The paper could be called a first chapter to the ‘vitiligo instruction manual,’” Spritz said. “We found that the vitiligo genetic risk score is higher in the multiplex families than in the simplex cases, and the more affected relatives in the family the higher the risk score. That means that vitiligo in multiplex families and simplex cases is basically the same, but that the families with multiple affected relatives have higher genetic risk. That means that the same treatments probably will be effective in both types of cases.”

Cropped back view of beautiful young European woman with skin condition that causes loss of melanin posing indoors. Slender slim female model in black tank top suffering from vitiligo disorder
A young woman posing who suffers from Vitiligo, an autoimmune disease that results in the loss of color in blotches of skin.

That finding complicates the ability of scientists and physicians who want to predict who might be affected by vitiligo. Simplex cases and multiplex cases seem to mostly involve the same underlying genetic variants, with different patients just having different combinations of genetic risk variants. Such a finding complicates the use of predictive personalized medicine to diagnose and treat complex diseases, Spritz said, because there doesn’t appear to be genetically-defined patient subgroups with different underlying biology who might thus respond differentially to personalized treatments.

In addition to Spritz, the authors of the article are Genevieve H.L. Roberts, a PhD candidate in human medical genetics and genomics at CU Anschutz Medical Campus at the time of writing the article; Subrata Paul, a PhD candidate in statistics at CU Denver; Daniel Yorgov, PhD, assistant professor of applied statistics at Purdue University Fort Wayne; and Stephanie Santorico, PhD, professor and director of statistical programs at the Colorado School of Public Health.

Second article

In the second article, which is published as a letter to the editor in the Journal of Investigative Dermatology, Spritz and his co-authors note that the average age of the onset of vitiligo in patients has changed dramatically over past decades.

“Vitiligo converted from being principally a pediatric-onset to principally an adult-onset disease over the period 1970-2004,” Spritz said. “That is amazing. Our genes haven’t changed over that period of time; altered genes or even gene effects don’t seem to be the cause. This must reflect some beneficial environmental change that somehow delays or reduces vitiligo triggering in people who are genetically susceptible. What was it? We don’t know.”

The authors write that one or more environmental changes seem to have altered triggering of vitiligo and delayed disease onset, with a similar pattern both in North America and in Europe. “While this apparently beneficial change provides an extraordinary inroad to discover vitiligo environmental triggers, the number of potential candidates is enormous,” Spritz and his colleagues write.

Among just a few of the possibilities in the United States: The Clean Air Acts of 1963 and 1970, the Nuclear Test Ban Treaty of 1963, the Water Quality Act of 1969, the establishment of the Occupational Safety and Health Administration in 1970. Globally, sunscreens with sun protection factor ratings were introduced in 1974. Even eating habits may contribute. The authors note that yogurt consumption became more common in the early 1970s, which potentially altered the gut microbiome for many people.

In addition to Spritz, the authors of the letter in Journal of Investigative Dermatology, are Ying Jin, MD, PhD, senior instructor of pediatrics, and Stephanie Santorico, PhD, professor and director of statistical programs at the Colorado School of Public Health.

Guest contributor: Mark Couch, School of Medicine. 

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Vitiligo researcher pushes limits in lab and in life

Richard Spritz on South Georgia island
Richard Spritz, MD, making the Shackleton Traverse, a trek across South Georgia island.

Geneticist Richard Spritz, MD, likes to be on the edge. Spritz, the Director of the University of Colorado School of Medicine’s (SOM) Human Medical Genetics and Genomics Program, loves the rush he gets from pushing his vintage Porsche 911 around a racetrack. He hikes in the Himalayas, and spent his most recent vacation trekking across a remote island, following the footsteps of famous Antarctic explorer Ernest Shackleton.

A career spent in a laboratory might seem less exciting, but not for Spritz. While he once was an accomplished mountain climber and survived two avalanches while backcountry skiing, he says his passion is not for taking risks—it is for the thrill of doing something new.

“I think that science is an incredibly adventurous thing. You’re always pushing beyond what’s known,” Spritz said. “I’m not an adrenaline junkie. Other people might call me that. I’ve just always been attracted to adventurous things.”

In Spritz’s eyes, there have been few bigger adventures in recent decades than the quest to understand  genetics and use that knowledge to cure diseases. After more than 40 years, he still marvels at how his career unfolded, and how far the science has come.

Fateful decisions

Spritz, 66, is one of the world’s leading vitiligo researchers. For almost two decades, he’s been conducting groundbreaking work understanding the genetics behind the skin pigmentation disorder that causes white patches to appear on the face, body and hair. An estimated 50 million people worldwide have the condition.

Spritz didn’t set out to become a geneticist. Two decisions he made while he was still a self-described “brash young man” shaped the course of his career.

Richard Spritz car
Among Spritz’s hobbies is racing his vintage Porsche 911

Spritz is from Philadelphia, but he felt the mountains’ call at a young age, and he became an accomplished mountain climber in his youth. Successful ascents in the Alps, including the notoriously dangerous north face of the Eiger, earned him the respect of the climbing elite, and in the 1970s he was invited to join an expedition to climb Mount Everest.

Spritz declined because he was in medical school and did not want to disrupt his career. “I absolutely made the right choice,” he said.

“It’s mostly out of my system,” Spritz said. But he’s not through going on adventures, and last fall he hiked across South Georgia, an island near Antarctica. Peter Hillary and Jamling Tengzing Norgay, the sons of the first two men to climb Everest, were on the trek. They were filming a documentary for National Geographic about Shackleton, who had to cross the mountainous island to rescue his stranded crew. In the company of climbing royalty, it was natural to think about Everest, but Spritz saw the risk.

“I’m 66 years old. While I’m not like most 66-year-olds, I know I could get high enough to get into real trouble,” Spritz said. Now, he gets his thrills through amateur auto racing, which he points out is far safer than climbing or extreme skiing. His next trip will be to the Himalayas for another trek.

Spritz made his second career-defining decision “literally one day while walking down the street,” he said. He had planned to become a surgeon and had made arrangements to start down that path, but realized genetic research was a better fit for someone seeking to push scientific boundaries.

“I was incredibly lucky, because I did that at exactly the right moment in history, at the beginning of recombinant DNA research,” Spritz said. “I was lucky to get in on the ground floor.”

It led to a fruitful career. In the late 1970s, researchers were just discovering how to isolate, identify and sequence human genes. The biggest early discovery Spritz was part of was finding and sequencing a mutation that affects hemoglobin, the molecule that carries oxygen in the blood. It was the first time a mutation had been sequenced.

Still making discoveries

“Despite the fact that vitiligo has been known for hundreds of years, there’s never been a drug developed for it,” Spritz said. “That might change in the near future.”

Spritz has not stopped researching—or making discoveries. In October, Spritz and his lab published a paper in Nature Genetics finding 23 genes linked to susceptibility for vitiligo. The lab tested 4,680 people with the condition and 39,586 control cases. The study attracted the attention of pharmaceutical companies, which Spritz said is good news because a medication to treat vitiligo could be a major step forward from the current steroid and ultraviolet light treatments.

“Despite the fact that vitiligo has been known for hundreds of years, there’s never been a drug developed for it,” Spritz said. “That might change in the near future.”

Much more research would be needed before a drug could be developed, and then it would have to go through rounds of safety and efficacy testing. Spritz said enough work has been done that complex relationships between genes “are coming together in a way that kind of makes sense,” which has allowed vitiligo researchers to “leap frog” ahead faster than Spritz expected.

People with other conditions might benefit as well. In the mid-2000s, Spritz established that vitiligo was an autoimmune disease, in which the body attacks its own skin pigmentation cells. Research has shown people susceptible to vitiligo have increased odds of other autoimmune conditions such as Type I diabetes, rheumatoid arthritis and Addison’s disease. Vitiligo research could lead to progress understanding those conditions, and vice versa.

That would be the next chapter in an ongoing scientific adventure.

“It’s amazing to me how far we’ve come, how naïve we were and yet how prescient we were at the same time,” Spritz said. “We are asking and answering the kinds of questions we couldn’t have imagined when I was a student. I think that’s incredibly inspirational – and we’ve hardly started.”

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