POSTER NO: 387

Identification of a novel psoriasis susceptibility locus at 4q and confirmation of linkage at 6p(PSORS1) by genome-wide scan in Chinese Hans

¹Xuejun Zhang, ¹Pingping He, ¹Zaixing Wang, ²Jing Zhang, ²Yuebin Li, ¹Hongyan Wang, ¹Shengcai Wei, ¹Shanyu Chen, ²Shijie Xu, ²Li Jin, ¹Sen Yang, ²Wei Huang
¹Institute of Dermatology, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, P.R. China, ²Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Shanghai 201203, P.R. China

Psoriasis is a heterogeneous disease with 7 major psoriasis susceptibility loci reported so far on chromosomes 1p, 1q, 3q, 4q, 6p, 17q and 19p respectively. To investigate the psoriasis susceptibility loci in Chinese Hans, a genome-wide scan was performed with two-point and multi-point parametric and nonparametric linkage analyses in 64 multiplex families who were Chinese Hans residing in east and southeast China, comprising 197 affected and 175 unaffected individuals. We detected evidence for linkage at 6p21 (PSORS1) with a two-point nonparametric linkage score (NPL)=3.90 (p=0.00016) and a maximum peak of multi-point NPL=4.13 (p=0.00009) when all families included. Parametric analysis revealed a heterogeneity LOD score (HLOD) of 5.16 under the assumption of a dominant model and 67% as the proportion of linked families. We could not confirm a previous reported locus (PSORS3) on distal chromosome 4q; however, a region of significant linkage was identified proximal to this proposed locus. A maximum LOD score of 3.70 and a HLOD score of 4.35 with the proportion of linked families = 85% were observed at marker D4S1597 with parametric linkage analysis. Multipoint nonparametric analysis demonstrated NPL scores greater than 3 throughout a region between 152.3cM and 172.3cM (from pter) with a maximum peak of 3.73 (p=0.00026) at 157.9 cM which locates D4S413. Our results showed that chromosomes 6p and 4q contained genes involved in the susceptibility to psoriasis vulgaris in a Chinese Han population. Other regions with weaker evidence for linkage could also hide minor susceptibility genes.