Genetic biomarkers for atopic dermatitis (AD) vary from one ethnic group to another, with a mutation in the interleukin-17 receptor A (THE 17TH) gene particularly important in Korean patients, the researchers say.
The finding takes researchers one step further in the effort to find 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 believe that if there is any method to simultaneously detect variations in the AD gene, the development of AD and then atopic gait could be prevented,” he said. Eung Ho Choi, MD, PhD, Professor of Dermatology at Yonsei University in Wonju, South Korea.
He presented the finding at the annual meeting of the International Society of Atopic Dermatitis (ISAD) 2021.
Atopic dermatitis is not caused by a single genetic mutation. But genetic factors play an important role, with approximately 75% concordance between monozygotic twins and only 23% for dizygotic twins.
“Genetic biomarkers are needed to predict the occurrence, severity, and response to treatment,” in addition to 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 to filaggrin gene variation, which can produce a defective skin barrier, Choi said. Others are involved in the immune response.
Although variations in the file gen filaggrina (FLG) are the most reliable genetic predictor of atopic dermatitis in Korean patients, they are less common in Korean patients than in northwestern European, Chinese, and Japanese patients. In Korean patients, the most common mutations in this gene are 3321dA and K4022X, Choi said.
To find out what other genetic variants are important in Korean patients with atopic dermatitis, Choi and colleagues developed the reverse transfer hybridization assay (REBA) to detect variations in the skin barrier to FLG , SPINK5 i KLK7 genes involved in variations in the immune response, KDR, 5RA, 9, DEFB1 (Defensin beta 1), 12RB1(interleukin-12 beta 1 receptor subunit) i 12RB2.
They compared the prevalence of these variations in 279 Koreans with atopic dermatitis with the prevalence in 224 healthy people without atopic dermatitis, and found that the probability of atopic dermatitis increased with the number of these variants: people with three or four variants. they had a 3.75 times higher risk of AD, and those with 5 or more variants had a 10.3 times higher risk. However, the number of variants did not correlate with the severity of the disease.
Filaggrin variation was present in 13.9% of people with atopic dermatitis. Approximately a quarter (28%) of patients with AD who had this variation had it impetigen, 15% had eczema herpeticum, and 5% had it prurigo nodularis. In comparison, 14% of patients with AD who did not present with this variation had impetigo and 5% had eczema herpeticum, but 19% had prurigo nodularis.
In a separate study, Choi and colleagues identified a mutation in THE 17TH , present in 8.1% of 332 patients with AD compared with 3.3% of 245 controls. Patients with THE 17TH all mutations had extrinsic AD.
The variation was associated with a longer, more frequent duration of the disease keratosis pillar, higher eosinophil counts in the blood, higher serum levels of total immunoglobulin (IgE), higher levels of IgE-specific IgE allergens in house mites and a greater need for systemic treatment than patients without THE 17THmutation.
These findings are important for advancing the treatment of atopic dermatitis, as the mechanism differs among patients. Emma Guttman-Yassky, MD, PhD, director of the Center of Excellence in Eczema and professor and professor of dermatology at the Icahn School of Medicine in Mount Sinai, New York.
“It has no single size in atopic dermatitis. And we need better markers that can tell us which treatment will work best for each patient,” he said. Medscape Medical News.
In addition to genetic biomarkers, she and her colleagues are analyzing proteins involved in inflammation. And they use strips of duct tape to harvest these markers, a less invasive approach than skin biopsies.
Annual meeting of the International Society for Atopic Dermatitis (ISAD) 2021:
Session 4. Presented on April 19, 2021.
Choi and Guttman-Yassky have not revealed any relevant financial relationship.
Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, newspapers, public radio and websites. He is working on a novel about alternative realities in physics. Harrison teaches writing in the Writers’ Grotto. Visit it at www. lairdharrison.com or follow him Twitter: @LairdH