Cytogenetic location: 3q21 Genomic coordinates (GRCh38): 3:126,100,000-129,500,000▼ MappingEnlund et al. (1999) performed a pairwise linkage study in search ...
Cytogenetic location: 3q21 Genomic coordinates (GRCh38): 3:126,100,000-129,500,000
Enlund et al. (1999) performed a pairwise linkage study in search of psoriasis susceptibility regions. A preliminary scan was performed on 20 families, yielding indications of linkage to 3q21. This region was further investigated using material from a total of 104 families, resulting in a nonparametric linkage (NPL) of 1.77. The material was stratified in families whose parental origin was in southwest Sweden. A maximum NPL value of 2.77 was obtained in this group. A transmission disequilibrium test (TDT) was performed on the stratified material and a significant P value of 0.005 was obtained at marker D3S1269. The locus was confirmed with TDT in replicate material consisting of 148 families in which a single member was affected, at marker D3S1551 (P = 0.0007).
▼ Molecular Genetics
Hewett et al. (2002) genotyped 644 individuals from 195 Swedish psoriatic families for 19 SNPs across the PSORS5 locus on chromosome 3q21. Transmission disequilibrium testing detected alleles of 3 SNPs in significant association with disease (p less than 0.05). Hewett et al. (2002) sequenced a 160-kb interval encompassing the 3 SNPs and the SLC12A8 gene (611316). A 5-marker haplotype spanning the 3-prime half of the SLC12A8 gene was strongly associated with psoriasis (p = 3.8 x 10(-5)).
Huffmeier et al. (2005) studied 210 German psoriasis trios and a case-control group of 375 patients and 376 controls and detected an association for 6 SNPs and 3 linkage disequilibrium-based haplotypes of the SLC12A8 gene. Association was strongest for ss35527511 (p = 0.0008) and haplotype E2 (p = 0.00059) and was independent of the HLA-associated PSORS1 risk allele. Through extended haplotype analysis, Huffmeier et al. (2005) demonstrated that 2 independent association signals exist in SLC12A8.
Samuelsson et al. (2004) found no association between 2 SNPs in the CSTA gene (184600) and psoriasis among 11 Swedish patients with the disorder from families showing linkage to chromosome 3q21.
Among 107 unrelated patients with psoriasis and 216 controls, Vasilopoulos et al. (2008) observed an association between a synonymous 162T-C SNP in the CSTA gene and disease (OR = 3.45, p = 0.001). Analysis of a 3-SNP haplotype showed a significant association between psoriasis and CSTA -190T/+162C/+344C (CSTA TCC; p = 10(-6)). An independent study of 126 families with psoriasis confirmed overtransmission of the TCC haplotype (p = 0.0001). However, the TCC haplotype was only associated with psoriasis in individuals carrying the risk allele at the HLA-Cw6 locus (142840.0001) (OR = 2.23, p = 0.0002). The findings suggested an interaction between PSORS5 and PSORS1.