BACKGROUND Crohn’s disease(CD)is characterized by a multifactorial etiology and a significant impact of genetic traits.While NOD2 mutations represent well established risk factors of CD,the role of other genes is inc...BACKGROUND Crohn’s disease(CD)is characterized by a multifactorial etiology and a significant impact of genetic traits.While NOD2 mutations represent well established risk factors of CD,the role of other genes is incompletely understood.AIM To challenge the hypothesis that single nucleotide polymorphisms(SNPs)in the genes CLEC5 A and CLEC7 A,two members of the C-type lectin domain family of pattern recognition receptors,may be associated with CD.METHODS SNPs in CLEC5 A,CLEC7 A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays.Therefore,DNA samples from 175 patients and 157 healthy donors were employed.Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses.RESULTS In accordance with previous studies,rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD(allelic P values=0.0368 and 0.0474,respectively).Intriguingly,for genotype AA of rs1285933 in CLEC5 A,a potential association with CD(recessive P=0.0523;odds ratio=1.90)was observed.There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7 A.Variants of rs1285933 had no impact on CLEC5 A gene expression.In contrast,genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed.There is no statistical interactionbetween the tested SNPs of NOD2 and CLEC5 A,suggesting of a novel pathway contributing to the disease.CONCLUSION Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5 A with CD.The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.展开更多
文摘BACKGROUND Crohn’s disease(CD)is characterized by a multifactorial etiology and a significant impact of genetic traits.While NOD2 mutations represent well established risk factors of CD,the role of other genes is incompletely understood.AIM To challenge the hypothesis that single nucleotide polymorphisms(SNPs)in the genes CLEC5 A and CLEC7 A,two members of the C-type lectin domain family of pattern recognition receptors,may be associated with CD.METHODS SNPs in CLEC5 A,CLEC7 A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays.Therefore,DNA samples from 175 patients and 157 healthy donors were employed.Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses.RESULTS In accordance with previous studies,rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD(allelic P values=0.0368 and 0.0474,respectively).Intriguingly,for genotype AA of rs1285933 in CLEC5 A,a potential association with CD(recessive P=0.0523;odds ratio=1.90)was observed.There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7 A.Variants of rs1285933 had no impact on CLEC5 A gene expression.In contrast,genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed.There is no statistical interactionbetween the tested SNPs of NOD2 and CLEC5 A,suggesting of a novel pathway contributing to the disease.CONCLUSION Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5 A with CD.The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.
