Identification Of Psoriasis Susceptibility Loci By Genome-wide Scan

Background Psoriasis is a common chronic inflammatory and hyperproliferative skin disease with a strong genetic component. Psoriasis vulgaris is the most common type (>90%), while other clinical forms include guttate, erythrodermic and palmoplantar psoriasis. The disease is characterized by hyperproliferation in the epidermis, which results in red scaly patches mainly affecting the scalp, elbows and knees. Psoriasis prevalence ranges from 0 to 3% and shows a wide variability among ethnic groups. The estimated prevalence of psoriasis is 2% in the USA and northern Europe. In China, psoriasis affects 0.123% of the population and there have been more than 3,000,000 cases reported since 1984. Psoriasis is a heterogeneous disease with 7 major psoriasis susceptibility loci reported so far on chromosomes 6p (PSORS1), 17q (PSORS2), 4q (PSORS3), Iq (PSORS4), 3q (PSORS5), 19p (PSORS6), and Ip (PSORS7) respectively. Objective To search for psoriasis susceptibility loci in Chinese Population. Method A genome-wide scan was performed with two-point and multi-point parametric and nonparametric linkage analyses in 61 multiplex families who were Chinese Hans residing in east and southeast China, comprising 189 affected and 166 unaffected individuals.Results We detected evidence for linkage at 6p21 (PSORS1) with NPL scores > 3 in the range of 39.9-62.3 cM and a maximum multi-point NPL=4.58 (p=0.000032). Parametric analysis revealed a maximum two-point HLOD of 4.30 with 58% as the proportion of linked families (a) and a maximum multi-point HLOD of 4.25 (a=53%) under theassumption of a dominant model. We could not confirm a previous reported locus (PSORS3) on distal chromosome 4q; however, a region of highly suggestive linkage was identified proximal to this proposed locus. Multi-point nonparametric analysis demonstrated NPL scores greater than 3 throughout a region between 152.5cM and 165.IcM (from pter) with a maximum peak of 3.69 0=0.00033) at 157.9 cM which locates D4S413. A maximum multi-point HLOD score of 2.31(a = 46%) was reached at 163.1 cM. With two-point parametric linkage analysis, we observed the highest LOD score of 2.43 and HLOD score of 3.94(a = 77%) at marker D4S1597.Conclusion Our results showed that chromosomes 6p and 4q may contain 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.