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29-01-2012 | Genetics | Article

ADAM33 gene variants associated with psoriasis

Abstract

Free abstract

MedWire News: Variants in a disintegrin and metalloproteinase 33 gene (ADAM33) are associated with psoriasis in Han Chinese people, suggest study results.

Many previous studies have isolated variants on several genes, such as the interleukin 23 receptor gene, that are significantly associated with psoriasis.

"However, the combined effect of certain susceptibility loci cannot entirely account for the observed genetic predispositions to psoriasis, suggesting that psoriasis susceptibility is largely polygenic," write Yuzhen Li (Harbin Medical University, Heilongjiang, China) and colleagues in Dermatology.

Variants in ADAM33 have been linked to several immune-mediated disorders including asthma.

To test whether mutations in ADAM33 are also associated with psoriasis, Li and team recruited 400 Han Chinese patients with psoriasis and 398 controls without the condition to take part in their study.

The participants were genotyped for six single nucleotide polymorphisms (SNPs) - rs2787094, rs512625, rs528557, rs597980, rs612709, and rs677044 - in ADAM33 that have been putatively linked with psoriasis susceptibility in European and American populations.

As reported in Dermatology, the team found that C allele carriers (CC and CG genotypes) of the rs2787094 and rs528557 SNPs had increased risk for psoriasis compared with GG homozygotes.

The strongest association was for people with the CC genotype of rs2787094 who had a significant 2.54-fold increased risk for psoriasis compared with people with the AA genotype.

Of 12 haplotypes constructed from each patient's genotype for the six SNPs, three (H1, H3, and H5) were observed significantly more often in psoriasis patients versus controls and were therefore associated with an increased risk for the condition.

Li and team also found that people with the AA genotype for rs512625 and A-allele carriers (AA and GA genotypes) of the rs612709 SNP seemed to be protected against psoriasis. Haplotype H8 also showed evidence of being protective against the disease.

The strongest protective effect associated with an individual SNP genotype was for the rs612709 AA genotype, which reduced risk for psoriasis by a significant 41%.

"This study suggests an association between ADAM33 gene polymorphisms and psoriasis in the northeastern Chinese Han population, providing new information regarding diagnosis and therapeutic strategies for psoriasis," say Li et al.

"Further association and functional studies of additional ADAM33 SNPs and other genes are required in diverse ethnic large-sample populations to identify the genetic factors associated with psoriasis," they conclude.

By Helen Albert

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