Atopic Dermatitis Genes Vary With Ethnicity

Laird Harrison

April 29, 2021

Genetic biomarkers for atopic dermatitis (AD) vary from one ethnic group to another, with a mutation in the interleukin-17 receptor A (IL-17RA) gene particularly important in Korean patients, researchers say.

The finding moves researchers another step forward in the effort to figure out which patients are most at risk for the disease and who will respond best to which treatments.

"Because atopic dermatitis is considered a complex trait, we think if there is any method to detect AD gene variations simultaneously, it could be possible to prevent the development of AD and then the atopic march," said Eung Ho Choi, MD, PhD, a dermatology professor at Yonsei University in Wonju,  South Korea.

He presented the finding at the International Society of Atopic Dermatitis (ISAD) 2021 Annual Meeting.

Atopic dermatitis is not caused by a single genetic mutation. But genetic factors play an important role, with about 75% concordance between monozygotic twins vs only 23% for dizygotic twins.

"Genetic biomarkers are needed in predicting the occurrence, severity, and treatment response," as well as determining the prognosis of atopic dermatitis "and applying it to precision medicine," Choi said.

Researchers have identified multiple genetic variations related to atopic dermatitis. One of the most significant genetic contributions found so far is for the filaggrin gene variation, which can produce a defective skin barrier, Choi said. Others are involved in the immune response.

Although variations in the filaggrin gene (FLG ) are the most reliable genetic predictor of atopic dermatitis in Korean patients, they are less common in Korean patients than in Northwestern Europeans, Chinese, and Japanese patients. In Korean patients, the most common reported mutations of this gene are 3321delA and K4022X, Choi said.

To find out what other gene variants are important in Korean patients with atopic dermatitis, Choi and his colleagues developed the reverse blot hybridization assay (REBA) to detect skin barrier variations in the FLG, SPINK5 and KLK7 genes, and genes involved in immune response variations, KDR, IL-5RA, IL-9, DEFB1 (Defensin Beta 1), IL-12RB1 (interleukin-12 receptor subunit beta 1), and IL-12RB2.

They compared the prevalence of these variations in 279 Koreans with atopic dermatitis to the prevalence in 224 healthy people without atopic dermatitis, and found that the odds ratio for atopic dermatitis increased with the number of these variants: People with three or four variants had a 3.75 times greater risk of AD, and those with 5 or more variants had a 10.3 times greater risk. The number of variants did not correlate to the severity of the disease, however.

The filaggrin variation was present in 13.9% of those with atopic dermatitis. About a quarter (28%) of the patients with AD who had this variation had impetigo, 15% had eczema herpeticum, and 5% had prurigo nodularis. By comparison, 14% of the patients with AD who did not have this variation had impetigo, and 5% had eczema herpeticum, but 19% had prurigo nodularis.

In a separate study, Choi and his colleagues identified a mutation in IL-17RA, present in 8.1% of 332 patients with AD compared to 3.3% of 245 controls. The patients with IL-17RA mutations all had extrinsic AD.

The variation was associated with longer disease duration, more frequent keratosis pilaris, higher blood eosinophil counts, higher serum total immunoglobulin E (IgE) levels, higher house dust mite allergen-specific IgE levels, and a greater need for systemic treatment than patients without the IL-17RA mutation.

Such findings are important for progress in treating atopic dermatitis because the mechanism differs among patients, said Emma Guttman-Yassky, MD, PhD, director of the Center for Excellence in Eczema, and professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City.

"It's not one size fits all in atopic dermatitis. And we need better biomarkers that will be able to tell us which treatment will work best for each patient," she told Medscape Medical News.

In addition to genetic biomarkers, she and her colleagues are analyzing proteins involved in inflammation. And they are using adhesive tape strips to harvest these markers, a less invasive approach than skin biopsies.

International Society of Atopic Dermatitis (ISAD) 2021 Annual Meeting:
Session 4. Presented April 19, 2021.

Choi and Guttman-Yassky have disclosed no relevant financial relationships.

Laird Harrison writes about science, health and culture. His work has appeared in national magazines, in newspapers, on public radio and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers GrottoVisit him at www. or follow him on  Twitter: @LairdH

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