title: Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes.
abstract: 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.
authors.affiliation: Department of Medical Biology, University of Split School of Medicine, Split, Croatia. vboraska@mefst.hr
authors.forename: Vesna
authors.initials: V
authors.lastname: Boraska
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Mahamadou
authors.initials: M
authors.lastname: Diakite
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Day-Williams
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
mesh_terms: 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
chemical_list: D008233:Lymphotoxin-alpha
references.citation: Genes Immun. 2002 Jun;3(4):225-8
references.pmid: 12058258
references.citation: Acta Diabetol. 2009 Dec;46(4):339-43
references.pmid: 19367363
references.citation: Diabetologia. 2005 Oct;48(10):2013-7
references.pmid: 16132956
references.citation: J Clin Endocrinol Metab. 2003 Jun;88(6):2767-74
references.pmid: 12788886
references.citation: Nat Genet. 2002 Dec;32(4):650-4
references.pmid: 12426569
references.citation: Int J Epidemiol. 2006 Feb;35(1):34-41
references.pmid: 16155052
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1850-8
references.pmid: 19363130
references.citation: Nat Genet. 2005 Nov;37(11):1217-23
references.pmid: 16244653
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Nat Genet. 2009 Oct;41(10):1110-5
references.pmid: 19734900
references.citation: Diabetologia. 1998 Oct;41(10):1241-8
references.pmid: 9794114
references.citation: Trends Immunol. 2004 Jan;25(1):4-7
references.pmid: 14698276
references.citation: Biochem Biophys Res Commun. 2008 May 9;369(3):943-7
references.pmid: 18328809
references.citation: Nat Genet. 2008 Sep;40(9):1098-102
references.pmid: 18711366
references.citation: Science. 2007 Jun 1;316(5829):1341-5
references.pmid: 17463248
references.citation: Nat Genet. 2008 May;40(5):638-45
references.pmid: 18372903
references.citation: Am J Hum Genet. 2001 Sep;69(3):553-69
references.pmid: 11484155
references.citation: Genet Epidemiol. 2003 Dec;25(4):327-38
references.pmid: 14639702
references.citation: Diabetes. 2007 Jan;56(1):256-64
references.pmid: 17192490
references.citation: J Mol Med (Berl). 2004 Jul;82(7):477-83
references.pmid: 15175864
references.citation: Diabetes Metab. 1997 Sep;23(4):295-301
references.pmid: 9342542
references.citation: Atherosclerosis. 2002 Apr;161(2):317-25
references.pmid: 11888514
references.citation: Genes Immun. 2006 Jan;7(1):51-8
references.pmid: 16341054
references.citation: Diabetologia. 2005 Mar;48(3):445-51
references.pmid: 15729581
references.citation: Science. 2007 Jun 1;316(5829):1331-6
references.pmid: 17463246
references.citation: Curr Diab Rep. 2009 Apr;9(2):164-71
references.pmid: 19323962
references.citation: Am J Hum Genet. 2007 Aug;81(2):338-45
references.pmid: 17668382
references.citation: Science. 1993 Jan 1;259(5091):87-91
references.pmid: 7678183
references.citation: Diabetologia. 2007 Dec;50(12):2562-71
references.pmid: 17928988
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Immunogenetics. 2006 Jun;58(5-6):465-70
references.pmid: 16738941
references.citation: Diabetes. 1999 Dec;48(12):2475-9
references.pmid: 10580439
references.citation: Nature. 2007 Feb 22;445(7130):881-5
references.pmid: 17293876
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Nat Genet. 2007 Jul;39(7):906-13
references.pmid: 17572673
references.citation: Nat Genet. 2007 Jun;39(6):770-5
references.pmid: 17460697
references.citation: Science. 2007 Jun 1;316(5829):1336-41
references.pmid: 17463249