Association of TNF-α polymorphisms in Crohn disease

• Published in: Human immunology Vol. 66; no. 1; pp. 56 - 59
• Main Authors: Zipperlen, Katrin, Peddle, Lynette, Melay, Bill, Hefferton, Donna, Rahman, Proton
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2005
• Subjects: association studies; Crohn disease; Crohn Disease - etiology; Crohn Disease - genetics; DNA Primers - genetics; Genetic Linkage; Genetic Predisposition to Disease; Humans; Newfoundland and Labrador; Polymorphism, Single Nucleotide; TNF-α; Tumor Necrosis Factor-alpha - genetics; Newfoundland and Labrador; TNF-α; association studies; Crohn disease
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2004.10.004

Clinical and molecular studies implicate tumor necrosis factor alpha (TNF-α) as a key mediator in the initiation and propagation of Crohn disease (CD). Genetic associations have been documented between promoter polymorphisms of TNF-α and CD; however, these associations have not been universally replicated. In this study, we set out to examine the association of five promoter TNF-α polymorphisms in CD subjects from a founder population. In total, 128 CD subjects and 103 ethnically matched healthy controls were genotyped with time-of-flight mass spectrometry for the following five single nucleotide polymorphisms (SNPs) in the 5′ flanking region of TNF-α gene: -1031 (T→C), -863 (C→A), -857 (C→T), -308 (G→A), and -238 (G→A). Primer sequences, termination mixes, and multiplexing were determined with Sequenom SpectroDESIGNER software v1.3.4. The minor allele frequency for the TNF-α SNPs in subjects with CD and healthy controls, respectively, were -238 (5.5% vs. 5.3%); -308 (17.6% vs. 18.9%); -857 (5.1% vs. 7.8%); -863 (19.1% vs. 17.5%), and -1031 (24.6% vs. 22.8%). Thus, none of the TNF-α variants was associated with CD. Furthermore, no genotype/phenotype correlations were observed for the mutant allele of the TNF-α variants and selected clinical outcomes. In conclusion, there was no significant association for any of the TNF-α promoter polymorphism tested and CD in the Newfoundland population.