Capon F, Semprini S, Chimenti S, Fabrizi G, Zambruno G, Murgia S, Carcassi C, Fazio M, Mingarelli R, Dallapiccola B, Novelli G
Department of Biopathology, "Tor Vergata" University of Rome, Italy.
J Invest Dermatol. 2001 May;116(5):728-30. doi: 10.1046/j.1523-1747.2001.01311.x.
Psoriasis is a chronic skin disorder affecting approximately 2% of the Caucasian population. Family clustering of the disease is well established and nonparametric linkage analyzes have mapped disease susceptibility loci on chromosomes 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 this study, we have carried out a linkage disequilibrium analysis, in order to achieve a finer localization. We recruited 79 triads from continental Italy and typed them at five loci spanning the 1.6 Mb region generating the highest multipoint LOD scores in our previous linkage study. We observed significant evidence for association with D1S2346 marker (p = 0.004). Results consistent with this data were obtained by typing an independent sample that 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 sought further confirmation of our results by typing both samples with two novel markers (140J1C and 140J1D) flanking D1S2346. Marker 140J1D generated a p value of 0.003 in the continental Italy sample where a D1S2346/140J1D haplotype was found with a higher frequency among patients' chromosomes. Altogether our data indicate that the 1q21 susceptibility gene may be localized in the genomic interval spanned by D1S2346 and 140J1D. This report provides evidence supporting the refinement of a non-HLA psoriasis susceptibility locus.
银屑病是一种慢性皮肤疾病，约影响2%的白种人。该疾病的家族聚集现象已得到充分证实，非参数连锁分析已将疾病易感基因座定位在6号染色体短臂（PSORS1）和17号染色体长臂（PSORS2）上。2号染色体长臂、3号染色体长臂、4号染色体长臂（PSORS3）、8号染色体长臂、16号染色体长臂和20号染色体短臂也有未被证实的连锁证据。我们在1号染色体长臂21区（PSORS4）定位了一个额外的易感基因座。在本研究中，我们进行了连锁不平衡分析，以实现更精细的定位。我们从意大利大陆招募了79个三联体，并在跨越1.6 Mb区域的五个基因座上对其进行分型，这些基因座在我们之前的连锁研究中产生了最高的多点LOD分数。我们观察到与D1S2346标记显著相关的证据（p = 0.004）。通过对一个独立样本进行分型获得了与该数据一致的结果，该样本包括28例患者和56例对照，来自撒丁岛。事实上，D1S2346和D1S2715标记的p值均为0.02。我们通过用位于D1S2346两侧的两个新标记（140J1C和140J1D）对两个样本进行分型来进一步证实我们的结果。在意大利大陆样本中，标记140J1D产生的p值为0.003，在患者染色体中发现D1S2346/140J1D单倍型的频率更高。我们的数据总体表明，1号染色体长臂21区的易感基因可能位于由D1S2346和140J1D跨越的基因组区间内。本报告提供了支持细化非HLA银屑病易感基因座的证据。
