Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes.
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.


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.


RESULTS
We did not find any consistent SNP associations with T2D in the case-control or family-based datasets.


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
Vesna
V
Department of Medical Biology, University of Split School of Medicine, Split, Croatia. vboraska@mefst.hr
Rayner
Nigel W
NW
Groves
Christopher J
CJ
Frayling
Timothy M
TM
Diakite
Mahamadou
M
Rockett
Kirk A
KA
Kwiatkowski
Dominic P
DP
Day-Williams
Aaron G
AG
McCarthy
Mark I
MI
Zeggini
Eleftheria
E
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D008233:Lymphotoxin-alpha
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