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09-12-2010 | Psoriasis | Article

IFIH1 gene variant protects against psoriasis

Abstract

Free abstract

MedWire News: Researchers have identified a rare missense variant in the gene encoding the putative RNA helicase interferon induced with helicase C domain 1 (IFIH1) that may help protect against psoriasis.

Further investigation of the role of IFIH1 in the pathogenesis of psoriasis may therefore provide new targets for pharmacological treatment of the condition, say Yonghong Li (Celera, Alameda, California, USA) and colleagues.

The researchers carried out a large-scale genetic association study testing 25,215 putative functional single nucleotide polymorphisms in three independent White psoriasis case-control sample sets.

They validated previous findings for three psoriasis genes, interleukin (IL)12B, IL23R, and IL13, and prioritized the remaining 337 markers for additional genotyping and association testing.

In all, 113 markers were associated with psoriasis risk, and the most significant association was seen for rs35667974 in the IFIH1 gene on chromosome. Another SNP on this gene - rs10930046 - was also significantly associated with psoriasis.

Both markers are missense polymorphisms that result in Ile923Val and His460Arg variants, respectively.

A total of 8.1% of participants without psoriasis and 3.9% of those with the skin condition were carriers of at least one of the minor, protective alleles 923Val or 460Arg. The frequency of both minor alleles was low, however, occurring in a respective 2.2% and 2.1% of participants without psoriasis.

The team reports in the Journal of Investigative Dermatology that carriers of the minor allele 923Val of rs35667974 were 57% less likely to develop psoriasis than noncarriers, while carriers of the minor allele460Arg of rs10930046 were 49% less likely.

The two markers had independent effects, so compared with individuals homozygous for both the 460His and 923Ile variants of the IFIH1 gene, carriers of the protective variants 923Val and/or 460Arg were 54% less likely to develop psoriasis.

Li et al note that there is also biological evidence for a role of IFIH1 in psoriasis, given that it affects cell growth, differentiation, and death. It has also been implicated in the recognition of RNA viruses, and virus infection may be one environmental factor that triggers or worsens psoriasis.

"Our genetic results suggest that understanding how the identified missense variants differentially affect IFIH1 protein function is important," the researchers conclude.

"Elucidation of their functional differences will provide insights into the role of IFIH1 in the pathogenesis of psoriasis and may guide the design of pharmacological interventions either directly or indirectly targeting IFIH1 for the treatment of psoriasis and other autoimmune and inflammatory diseases."

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 Lucy Piper

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