Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden

Abstract

We have performed a pair-wise linkage study in the search for psoriasis susceptibility regions. A preliminary scan was performed on 20 families. In this set we obtained indications of linkage on chromosome 3q21. This region was further investigated using material from a total of 104 families (set 1B) resulting in a non-parametric linkage (NPL) of 1.77. The material was stratified in families whose parental origin is in southwest Sweden (set 1C). A maximum NPL value of 2.77 was obtained in this group. A transmission disequilibrium test (TDT) was performed on the stratified material (set 1C) 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 (P value 0.0007) at marker D3S1551. Thus, we have observed a significant P value using TDT in the vicinity of markers D3S1269/D3S1551, suggesting a novel psoriasis susceptibility region.

Genetic epidemiology of psoriasis and psoriatic arthritis

“…The psoriasis susceptibility loci that have been mapped using linkage methods include: PSORS1 on 6p21.3, PSORS2 on 17q, PSORS3 on 4q, PSORS4 on 1cen-q21, PSORS5 on 3q21, PSORS6 on 19p, PSORS7 on 1p, and PSORS9 on 4q31. [20][21][22][23][24][25][26][27] Additional putative psoriasis candidate loci have been reported on 16q and 20p. 28 The loci on 6p and 17q have been replicated with independent linkage studies.…”

The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation

“…The genetic specificity and stability of the population of western Sweden has also been reported for other genetic disorders such as carbohydrate deficient glycoprotein syndrome type 1A (CDG1A) 28 and psoriasis. 29 We would have expected the 3171ins5 mutation to have appeared in Denmark since the geographical closeness is apparent (Figure 3), but also for historical reasons, the south-western parts of Sweden belonged to Denmark from the middle ages until the 17th century. However no 3171ins5 has been detected in Danish breast and/or ovarian cancer families (Dr A Ê ke Borg, personal communication).…”

Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus

“…Evidence has been reported for additional susceptibility loci on chromosomes 17q (PSORS2), 4q (PSORS3), 1q (PSORS4), 3q (PSORS5), 19p (PSORS6) and 1p (PSORS7). (Nair et al 1997;Matthews et al 1996;Capon et al 1999;Enlund et al 1999;Lee et al 2000;Veal et al 2001). PSORS4 was originally identified in an Italian population (Capon et al 1999) and later independent replication of this linkage was obtained in 2001 (Bowcock et al 2001).…”