An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians.
An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians.
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DOI：
10.1186/1471-2350-7-64
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发表时间：
2006-07-26
影响因子：
--
通讯作者：
Stewart G
中科院分区：
文献类型：
--
作者：
Bugeja MJ;Booth D;Bennetts B;Heard R;Rubio J;Stewart G
多发性硬化症(MS)是一种以炎症和神经元变性为特征的中枢神经系统(CNS)疾病。它被认为是由许多基因的复杂相互作用造成的，每个基因的影响都不大。趋化因子对细胞向炎症部位的迁移至关重要，包括中枢神经系统，许多与MS的发病机制有关。大多数CC趋化因子基因被编码在染色体17q11.2-12上的一个簇中，该基因在许多全基因组筛查中被认为可能与MS相关。我们进行了两阶段分析以研究趋化因子基因簇与MS的关联。在对几个DNA池中的趋化因子基因进行测序以确定常见多态之后，在澳大利亚MS三个家系的队列中对12个候选单核苷酸多态(SNPs)进行了基因分型。在几个因素的分层后，确定了四个SNPs的轻微显著(未校正)传输失真。我们还使用两个独立的队列，确定了包含CCL2和CCL11基因的单倍型的轻微显著(未校正)传输失真，这与另一组最近的报告一致。我们的结果提示几种趋化因子可能与MS易感性有关，鉴于趋化因子及其受体是治疗药物的合适靶点，在这一领域有必要进行进一步的研究。
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. It is believed to result from the complex interaction of a number of genes, each with modest effect. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS. We conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. After sequencing the chemokine genes in several DNA pools to identify common polymorphisms, 12 candidate single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of Australian MS trio families. Marginally significant (uncorrected) transmission distortion was identified for four of the SNPs after stratification for several factors. We also identified marginally significant (uncorrected) transmission distortion for haplotypes encompassing the CCL2 and CCL11 genes, using two independent cohorts, which was consistent with recent reports from another group. Our results implicate several chemokines as possibly being associated with MS susceptibility, and given that chemokines and their receptors are suitable targets for therapeutic agents, further investigation is warranted in this region.
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