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08-07-2010 | Dermatology | Article

Innate and adaptive immunity genes implicated in alopecia areata

Abstract

Free abstract

MedWire News: Results from a genome-wide association study show an association between genes involved in innate and adaptive immunity and susceptibility to alopecia areata (AA).

"Finding the initial genes underlying AA is a big step forward, but the nature of the genes is even more exciting," said study author Angela Christiano, from Columbia University Medical Center in New York, USA.

"Finally, we have the possibility of developing drugs that specifically target the mechanism behind the disease."

The researchers enrolled 1054 people with AA and 3278 controls to take part in the study.

They found a total of 139 single nucleotide polymorphisms (SNPs) that were significantly associated with AA. Population-attributable risks for the risk alleles of each SNP showed contributions ranging from 16% to 69%.

"These findings demonstrate an overwhelming contribution of risk from genetic factors in AA, which awaits confirmation in a validation study," say the authors.

The majority of the SNPs clustered into eight genomic regions on chromosomes 2, 4, 6, 9, 10, and 12.

The regions included genes controlling the activation and proliferation of regulatory T cells; the cytotoxic T lymphocyte associated antigen 4 gene; the interleukin (IL)-2/IL-21 gene, IL-2 receptor A gene (IL-2RA);the Ikaros family zinc finger 4 gene ; and the human leukocyte antigen region. Other genes in the associated regions included those expressed in the hair follicle itself (PRDX5 and STX17).

There was also a strong association within the cytomegalovirus UL16-binding protein gene cluster, encoding activating ligands of the natural killer cell receptor NKG2D (KLRK1 gene), an area not previously associated with autoimmune disease.

"There seems to be a shared mechanism among organs that express NKG2D danger signals as part of the initiating process. And since drugs are already in development that target these pathways - because they are being tested to treat rheumatoid arthritis, Type 1 diabetes and other diseases where the NKG2D receptor is involved - we may soon be able to test these drugs in clinical trials for AA," said Christiano.

She added: "The advantage of this large sample size is that we can be sure that this group of genes was identified with a high statistical significance and did not happen by chance. The next step is to replicate this study in future research."

The results of this study are published in the journal Nature.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Helen Albert