Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
1 Department of Medical Biology, University of Split School of Medicine, Split, Croatia
2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
3 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
4 Peninsula Medical School, University of Exeter, Exeter, UK
5 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
BMC Medical Genetics 2010, 11:69 doi:10.1186/1471-2350-11-69Published: 6 May 2010
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.
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.
We did not find any consistent SNP associations with T2D in the case-control or family-based datasets.
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.