The IDDM8 region on chromosome 6q27, first identified as a susceptibility locus for type 1 diabetes, has previously been linked and associated with rheumatoid arthritis (RA). The region contains a number of potential candidate genes, including programmed cell death 2 (PDCD2), the proteosome subunit beta type 1 (PSMB1), delta-like ligand 1 (DLL-1) and TATA box-binding protein (TBP) amongst others. The aim of this study was to fine map the IDDM8 region on chromosome 6q27, focusing on the genes in the region, to identify polymorphisms that may contribute to susceptibility to RA and potentially to other autoimmune diseases. Validated single nucleotide polymorphisms (SNPs; n = 65) were selected from public databases from the 330 kb region of IDDM8. These were genotyped using Sequenom MassArray genotyping technology in two datasets; the test dataset comprised 180 RA cases and 180 controls. We tested 50 SNPs for association with RA and any significant associations were genotyped in a second dataset of 174 RA cases and 192 controls, and the datasets were combined before analysis. Association analysis was performed by chi-square test implemented in Stata software and linkage disequilibrium and haplotype analysis was performed using Helix tree version 4.1. There was initial weak evidence of association, with RA, of a number of SNPs around the loc154449 putative gene and within the KIAA1838 gene; however, these associations were not significant in the combined dataset. Our study has failed to detect evidence of association with any of the known genes mapping to the IDDM8 locus with RA.

译文

:染色体6q27上的IDDM8区最初被确定为1型糖尿病的易感基因座,先前已与类风湿关节炎(RA)相关联并与之相关。该区域包含许多潜在的候选基因,包括程序性细胞死亡2(PDCD2),蛋白体亚基beta 1型(PSMB1),类δ配体1(DLL-1)和TATA盒结合蛋白(TBP)等。 。这项研究的目的是对6q27号染色体上的IDDM8区进行精细定位,重点关注该区中的基因,以鉴定可能导致RA易感性以及其他自身免疫性疾病易感性的多态性。从IDDM8的330 kb区域的公共数据库中选择经过验证的单核苷酸多态性(SNP; n = 65)。使用Sequenom MassArray基因分型技术在两个数据集中对它们进行基因分型。测试数据集包括180个RA病例和180个对照。我们测试了50个SNP与RA的关联,并在174个RA病例和192个对照的第二个数据集中对任何重要的关联进行了基因分型,并在分析前将这些数据集进行了合并。通过在Stata软件中实施的卡方检验进行关联分析,并使用Helix树版本4.1进行连锁不平衡和单倍型分析。最初很少有证据证明loc154449推定基因周围和KIAA1838基因内有许多SNP与RA相关。但是,这些关联在组合数据集中并不重要。我们的研究未能发现与RA映射到IDDM8基因座的任何已知基因相关的证据。

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