BACKGROUND: The TNF/LTA locus has been a long-standing T2D candidate gene. Several studies have examined association of TNF/LTA SNPs with T2D but the majority have been small-scale and produced no convincing evidence of association. The purpose of this study is to examine T2D association of tag SNPs in the TNF/LTA region capturing the majority of common variation in a large-scale sample set of UK/Irish origin.<br /><br />METHODS: This study comprised a case-control (1520 cases and 2570 control samples) and a family-based component (423 parent-offspring trios). Eleven tag SNPs (rs928815, rs909253, rs746868, rs1041981 (T60N), rs1800750, rs1800629 (G-308A), rs361525 (G-238A), rs3093662, rs3093664, rs3093665, and rs3093668) were selected across the TNF/LTA locus and genotyped using a fluorescence-based competitive allele specific assay. Quality control of the obtained genotypes was performed prior to single- and multi-point association analyses under the additive model.<br /><br />RESULTS: We did not find any consistent SNP associations with T2D in the case-control or family-based datasets.<br /><br />CONCLUSIONS: The present study, designed to analyse a set of tag SNPs specifically selected to capture the majority of common variation in the TNF/LTA gene region, found no robust evidence for association with T2D. To investigate the presence of smaller effects of TNF/LTA gene variation with T2D, a large-scale meta-analysis will be required.
Boraska, V., Rayner, N. W., Groves, C. J., Frayling, T. M., Diakite, M., Rockett, K. A., … Zeggini, E. (2010). Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes. BMC Medical Genetics, 11(1). https://doi.org/10.1186/1471-2350-11-69