Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21
Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21
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DOI：
10.1046/j.1523-1747.2001.01311.x
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发表时间：
2001-05-01
影响因子：
6.5
通讯作者：
Novelli, G
中科院分区：
文献类型：
--
作者：
Capon, F;Semprini, S;Novelli, G
牛皮癣是一种慢性皮肤病，影响大约2%的高加索人口。本病的家族聚集性已建立，非参数连锁分析已定位到6p(PSORS1)和17q(PSORS2)上的易感基因座，2q、3q、4q(PSORS3)、8q、16q和20p上也有未经证实的连锁证据，我们在1q21(PSORS4)上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，并在横跨1.6Mb区域的5个基因座上进行了打字，产生了我们之前的Linkage研究中最高的多点LOD分数。我们观察到与D1S2346标记相关的重要证据(p=0.004)。通过对来自撒丁岛的28名患者和56名对照的独立样本进行分型，获得了与这一数据一致的结果。事实上，D1S2346和D1S2715标记的p值均为0.02。我们用D1S2346两侧的两个新标记(140J1C和140J1D)进一步验证了我们的结果，标记140J1D在意大利大陆样本中产生的p值为0.003，在那里发现D1S2346/140J1D单倍型在患者染色体中出现的频率更高。综上所述，1q21易感基因可能位于D1S2346和140J1D跨越的基因组区间。这份报告提供了支持改进非人类白细胞抗原的牛皮癣易感基因的证据。
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.