AIMS/HYPOTHESIS: The proinflammatory cytokine TNF-alpha has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-alpha (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources. MATERIALS AND METHODS: The G-308A and G-238A TNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls. RESULTS: There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran-Mantel-Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16). CONCLUSIONS/ INTERPRETATION: The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.
AIMS/HYPOTHESIS: The proinflammatory cytokine TNF-alpha has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-alpha (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources. MATERIALS AND METHODS: The G-308A and G-238ATNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls. RESULTS: There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran-Mantel-Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16). CONCLUSIONS/ INTERPRETATION: The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.
Authors: John P A Ioannidis; Thomas A Trikalinos; Evangelia E Ntzani; Despina G Contopoulos-Ioannidis Journal: Lancet Date: 2003-02-15 Impact factor: 79.321
Authors: M J Simmonds; J M Heward; J M M Howson; H Foxall; R Nithiyananthan; J A Franklyn; S C L Gough Journal: Genes Immun Date: 2004-06 Impact factor: 2.676
Authors: T M E Davis; A D Wright; Z M Mehta; C A Cull; I M Stratton; G F Bottazzo; E Bosi; I R Mackay; R R Holman Journal: Diabetologia Date: 2005-02-24 Impact factor: 10.122
Authors: Chikh Bengra; Theodore E Mifflin; Yuri Khripin; Paolo Manunta; Scott M Williams; Pedro A Jose; Robin A Felder Journal: Clin Chem Date: 2002-12 Impact factor: 8.327
Authors: Diana I Vázquez-Huerta; Bertha A Alvarez-Rodríguez; Jorge F Topete-Reyes; José F Muñoz-Valle; Renato Parra-Michel; Francisco Fuentes-Ramírez; María A Salazar-López; Yeminia Valle; Zyanya Reyes-Castillo; A Cruz-González; Lorena M Brennan-Bourdon; Norma Torres-Carrillo Journal: Int J Clin Exp Med Date: 2014-08-15
Authors: Vesna Boraska; Nigel W Rayner; Christopher J Groves; Timothy M Frayling; Mahamadou Diakite; Kirk A Rockett; Dominic P Kwiatkowski; Aaron G Day-Williams; Mark I McCarthy; Eleftheria Zeggini Journal: BMC Med Genet Date: 2010-05-06 Impact factor: 2.103