Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21

Psoriasis is a chronic skin disorder affecting approximately 2% of the Cauc asian population. Family clustering of the disease is well established and nonparametric linkage analyzes have mapped disease susceptibility loci on c hromosomes 6p (PSORS1) and 17q (PSORS2), Nonconfirmed evidence for linkage is also available for chromosomes 2q 3q, 4q (PSORS3), 8q, 16q, and 20p, We mapped an additional susceptibility locus on chromosome 1q21 (PSORS4), In t his study, we have carried out a linkage disequilibrium analysis, in order to achieve a finer localization. We recruited 79 triads from continental It aly and typed them at five loci spanning the 1.6 Mb region generating the h ighest multipoint LOD scores in our previous Linkage study. We observed sig nificant evidence for association with D1S2346 marker (p = 0.004). Results consistent with this data were obtained by typing an independent sample tha t included 28 patients and 56 controls, originating from Sardinia. In fact, p values of 0.02 were observed with both D1S2346 and D1S2715 markers. We s ought further confirmation of our results by typing both samples with two n ovel markers (140J1C and 140J1D) flanking D1S2346, Marker 140J1D generated a p value of 0.003 in the continental Italy sample where a D1S2346/140J1D h aplotype was found with a higher frequency among patients' chromosomes. Alt ogether our data indicate that the 1q21 susceptibility gene may be localize d in the genomic interval spanned by D1S2346 and 140J1D. This report provid es evidence supporting the refinement of a non-HLA psoriasis susceptibility locus.