Investigation of the Chromosome 17q25 PSORS2 Locus in Atopic Dermatitis

• Published in: Journal of investigative dermatology Vol. 126; no. 3; pp. 603 - 606
• Main Authors: Morar, Nilesh, Bowcock, Anne M., Harper, John I., Cookson, William O.C.M., Moffatt, Miriam F.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-03-2006; Nature Publishing; Elsevier Limited
• Subjects: Acetyltransferases - genetics; Allergic diseases; Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 17; Dermatitis, Atopic - genetics; Dermatology; Genetic Linkage; Haplotypes; Humans; Immunopathology; Medical sciences; Phosphoproteins; Polymorphism, Single Nucleotide; Skin allergic diseases. Stinging insect allergies; Sodium-Hydrogen Exchangers - genetics; Human; Allergy; Immunopathology; Skin disease; Chromosome E17; Atopic dermatitis; Dermatology; Genetics; Locus; Atopy
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/sj.jid.5700108

Psoriasis and atopic dermatitis (AD) are strongly genetic and inherited as multi-factorial traits. In both diseases, linkage has been reported to chromosome 17q25. For psoriasis, the locus has been labelled PSORS2. Two peaks of association here contain the psoriasis candidate genes SLC9A3R (solute carrier family 9, isoform 3 regulatory factor), NAT9 (N-acetyltransferase superfamily), and RAPTOR (rapamycin (TOR)). We genotyped 14 of the most significantly associated single-nucleotide polymorphisms (SNPs) in these genes in a panel of 148 families (ECZ1) identified through a proband with active AD. The panel contains 350 siblings and 245 sib-pairs. Replication of positive findings was sought in a second panel, MRC-E, comprising of 278 families, 634 siblings, and 470 sib-pairs. SNP genotyping was carried out by Sequenom MassArray technology. Using family-based tests of association (transmission disequilibrium test), rs878906, in intron 3 of NAT9, was significantly associated with AD (P=0.010) in the ECZ1 panel. In the MRC-E panel, rs895691, between the end of exon 6 of SLC9A3R1 and exon 7 of NAT9, was associated with AD (P=0.037). These were not significant when multiple comparisons were taken into account. Haplotype analysis revealed no significant associations in either population. These results suggest that the psoriasis candidate genes do not account for previously observed linkage of the 17q25 PSORS2 locus to AD.