Traks Tanel, Koido Kati, Eller Triin, Maron Eduard, Kingo Külli, Vasar Veiko, Vasar Eero, Kõks Sulev
Department of Physiology, University of Tartu, Ravila 19, 50411 Tartu, Estonia.
BMC Med Genet. 2008 Dec 16;9:111. doi: 10.1186/1471-2350-9-111.
Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD.
Case-control association study was performed with seven SNPs from the IL10 gene cluster. 153 patients with MDD and 277 healthy control individuals were recruited.
None of the selected SNPs were individually associated with MDD. The linkage disequilibrium (LD) analysis indicated the existence of two recombination sites in the IL10 gene cluster, thus confirming the formerly established LD pattern of this genomic region. This also created two haplotype blocks, both consisting of three SNPs. Additionally, the haplotype analysis detected a significantly higher frequency of block 2 (IL20 and IL24 genes) haplotype TGC in the patients group compared to healthy control individuals (P = 0.0097).
Our study established increased risk for MDD related to the IL20 and IL24 haplotype and suggests that cytokines may contribute to the pathogenesis of MDD. Since none of the block 2 SNPs were individually associated with MDD, it is possible that other polymorphisms linked to them contribute to the disease susceptibility. Future studies are needed to confirm the results and to find the possible functional explanation.
先天性免疫炎症反应被认为在重度抑郁症(MDD)的发病机制中起作用。白细胞介素(IL)-10家族细胞因子IL-10、IL-19、IL-20和IL-24均与炎症过程有关,各自基因中的多态性与各种免疫病理状况相关。本研究旨在调查这些基因中的单核苷酸多态性(SNP)是否也与MDD相关。
对IL10基因簇中的7个SNP进行病例对照关联研究。招募了153例MDD患者和277名健康对照个体。
所选的SNP均未单独与MDD相关。连锁不平衡(LD)分析表明IL10基因簇中存在两个重组位点,从而证实了该基因组区域先前确立的LD模式。这也产生了两个单倍型块,均由三个SNP组成。此外,单倍型分析检测到患者组中第2个块(IL20和IL24基因)单倍型TGC的频率显著高于健康对照个体(P = 0.0097)。
我们的研究确定了与IL20和IL24单倍型相关的MDD风险增加,并表明细胞因子可能在MDD的发病机制中起作用。由于第2个块中的SNP均未单独与MDD相关,与它们连锁的其他多态性可能导致疾病易感性。需要进一步的研究来证实结果并找到可能的功能解释。