Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2

被引:24
作者
Abad, C. [1 ]
Gonzalez-Escribano, M. F. [1 ]
Diaz-Gallo, L. M.
Lucena-Soto, J. M. [1 ]
Marquez, J. L. [2 ]
Leo, E. [2 ]
Crivell, C. [2 ]
Gomez-Garcia, M. [3 ]
Martin, J. [4 ]
Nunez-Roldan, A. [1 ]
Garcia-Lozano, J. R. [1 ]
机构
[1] Hosp Univ Virgen del Rocio, Inst Biomed, Serv Inmunol, Seville 41013, Spain
[2] Hosp Univ Virgen del Rocio, Serv Aparato Digest, Seville 41013, Spain
[3] Hosp Univ Virgen de las Nieves, Unidad Enfermedad Inflamatoria Intestinal, Granada, Spain
[4] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain
关键词
genetic association; Crohn's disease; Toll-like receptors; TLR10; gene; NOD2/CARD15; gene-gene interactions; SEQUENCE VARIANTS; PEPTIDOGLYCAN; RECOGNITION; FREQUENCIES;
D O I
10.1038/gene.2011.41
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio = 1.89, P-value = 0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG) haplotype (P-c < 0.0001). The interaction gain attributed to the combination of both genes was negative (IG= -2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes. Genes and Immunity (2011) 12, 635-642; doi:10.1038/gene.2011.41; published online 30 June 2011
引用
收藏
页码:635 / 642
页数:8
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