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Article

Cutaneous psoriasis, psoriatic arthritis genetic differences revealed

Author(s):

Researchers have uncovered new information about the pathogenetic similarities and differences between cutaneous psoriasis and psoriatic arthritis in a recent study. They hope the information, one day, leads to a test to help doctors determine which psoriasis patients will advance with psoriatic disease.

Researchers have uncovered new information about the pathogenetic similarities and differences between cutaneous psoriasis and psoriatic arthritis in a recent study.1

“We were able to identify genetic differences between psoriasis of the skin and psoriatic arthritis. Psoriasis is often used as a term that doesn’t discriminate the two conditions, and that has been a barrier to research,” said the study’s senior author James T. Elder, M.D., Ph.D., Kirk D. Wuepper professor of molecular genetic dermatology, department of dermatology, at the University of Michigan, Ann Arbor.

What makes this study different than earlier studies, according to Dr. Elder, is the researchers studied thousands of people based on two disease definitions. They created a working definition for purely cutaneous psoriasis - a subject who, at the time of study enrollment, had cutaneous psoriasis for 10 years without having developed joint complaints. They also created a working definition for psoriatic arthritis - a person who has psoriasis but a rheumatologist has also characterized the nature of their arthritis and determined the arthritis is due to psoriasis.

Dr. Elder and colleagues then looked for small differences between the frequency of alleles, or genetic variations, between those groups.  

READ: Gene mutation finding could lead to pustular psoriasis therapy

They found a number of interesting differences in several genes that are relevant to immune function.

“The major effect has to do with genes in a region of the genome, or chromosome 6, that’s called the Major Histocompatibility Complex (MHC). It contains about 200 genes. About six of them, called HLA genes, are particularly important in individualizing each person’s immune response,” Dr. Elder said.

About one fourth of people who develop psoriasis, overall, eventually go on to develop psoriatic arthritis, according to Dr. Elder.

“Doctors who care for psoriasis patients would really like to know which ones will develop the arthritis and which will not. The reason that is important is maybe they would treat somebody slightly differently, perhaps more intensively, if they knew the person was destined to get arthritis,” he said. “We feel that the genetic differences that we’ve outlined in this paper and also in our 2014 paper, will, when combined with other studies … someday, before too long, result in a test that would help doctors know which patients would get the arthritis and which would not.”2

READ: Gene helps confirm existence of psoriatic arthritis

That’s the implication for dermatologists, he said. For scientists, the study points to different biological pathways that could influence whether or not a person gets the disease, and that’s useful for understanding the disease, he said.

“As doctors have known, these two diseases have a lot in common, but there are some differences that have to do with what gene versions people happen to get,” Dr. Elder says.

Disclosure: Dr. Elder reports no relevant disclosures.

References:

1. Stuart PE, Nair RP, Tsoi LC, Tejasvi T, Das S, Kang HM, Ellinghaus E, Chandran V, Callis-Duffin K, Ike R, Li Y, Wen X, Enerbäck C, Gudjonsson JE, Kõks S, Kingo K, Esko T, Mrowietz U, Reis A, Wichmann HE, Gieger C, Hoffmann P, Nöthen MM, Winkelmann J, Kunz M, Moreta EG, Mease PJ, Ritchlin CT, Bowcock AM, Krueger GG, Lim HW, Weidinger S, Weichenthal M, Voorhees JJ, Rahman P, Gregersen PK, Franke A, Gladman DD, Abecasis GR, Elder JT. Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture. Am J Hum Genet. 2015 Dec 3;97(6):816-36. 

2. Okada Y, Han B, Tsoi LC, Stuart PE, Ellinghaus E, Tejasvi T, Chandran V, Pellett F, Pollock R, Bowcock AM, Krueger GG, Weichenthal M, Voorhees JJ, Rahman P, Gregersen PK, Franke A, Nair RP, Abecasis GR, Gladman DD, Elder JT, de Bakker PI, Raychaudhuri S. Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes. Am J Hum Genet. 2014 Aug 7;95(2):162-72. 

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