银屑病与在II型糖尿病和克罗恩病中鉴定出的多效性易感基因座相关。

Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease.

作者信息

Wolf N, Quaranta M, Prescott N J, Allen M, Smith R, Burden A D, Worthington J, Griffiths C E M, Mathew C G, Barker J N, Capon F, Trembath R C

出版信息

J Med Genet. 2008 Feb;45(2):114-6. doi: 10.1136/jmg.2007.053595. Epub 2007 Nov 9.

DOI:10.1136/jmg.2007.053595

PMID:17993580

Abstract

BACKGROUND

Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage analyses have clearly mapped a primary disease susceptibility locus to the major histocompatibility complex (MHC) region on chromosome 6p21. More recently, whole-genome association studies have identified two non-MHC disease genes (IL12B and IL23R), both of which also confer susceptibility to Crohn disease (CD).

OBJECTIVE AND METHODS

To ascertain the genetic overlap between these two inflammatory conditions further, we investigated 15 CD-associated loci in a psoriasis case-control dataset.

RESULTS

The analysis of 1256 patients and 2938 unrelated controls found significant associations for loci mapping to chromosomes 1q24 (rs12035082, p = 0.009), 6p22 (rs6908425, p = 0.00015) and 21q22 (rs2836754, p = 0.0003). Notably, the marker showing the strongest phenotypic effect (rs6908425) maps to CDKAL1, a gene also associated with type 2 diabetes.

CONCLUSIONS

These results substantiate emerging evidence for a pleiotropic role for s genes that contribute to the pathogenesis of immune-mediated disorders.

摘要

背景

银屑病是一种免疫介导的皮肤病，以多因素性状遗传。连锁分析已明确将一个主要疾病易感基因座定位到6号染色体p21区域的主要组织相容性复合体（MHC）。最近，全基因组关联研究已鉴定出两个非MHC疾病基因（IL12B和IL23R），这两个基因也赋予克罗恩病（CD）易感性。

目的和方法

为了进一步确定这两种炎症性疾病之间的遗传重叠，我们在一个银屑病病例对照数据集中研究了15个与CD相关的基因座。

结果

对1256例患者和2938名无关对照的分析发现，定位到1号染色体q24（rs12035082，p = 0.009）、6号染色体p22（rs6908425，p = 0.00015）和21号染色体q22（rs2836754，p = 0.0003）的基因座存在显著关联。值得注意的是，表现出最强表型效应的标记（rs6908425）定位于CDKAL1，该基因也与2型糖尿病相关。