OBJECTIVE: Regulated on activation, normal T-cell expressed and secreted (RANTES)/chemokine(C-C motif) ligand (CCL5) is expressed by adipocytes, and serum levels of RANTES are increased in obesity and type 2 diabetes. The aim of this study was to test the hypothesis that RANTES is involved in the pathogenesis of type 2 diabetes by analyzing the triangular association between CCL5 gene polymorphisms, systemic RANTES concentrations, and incident type 2 diabetes in a large prospective study. SUBJECTS AND METHODS: The study is based on 502 individuals (293 men and 209 women) and 1632 individuals (859 men and 773 women) with and without incident type 2 diabetes from the population-based MONItoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) case-cohort study respectively (mean follow-up time+/-s.d. 10.1+/-4.9 years). CCL5 genotypes and RANTES serum concentrations were determined and associations between genotypes, haplotypes, serum levels, and incident type 2 diabetes were assessed. Results Minor alleles of four single nucleotide polymorphisms were associated with lower RANTES levels (P(additive) between 1.2 x 10(-9) and 3.1 x 10(-8)), but neither genotypes, haplotypes, nor serum levels were associated with incident type 2 diabetes. CONCLUSIONS: Our data suggest that RANTES/CCL5 gene variants and serum levels are not causally related with type 2 diabetes and that elevated RANTES levels in patients with type 2 diabetes may be a consequence of hyperglycemia. However, our findings cannot preclude a local role in adipose tissue where RANTES expression may contribute to leukocyte infiltration and a proinflammatory state.
OBJECTIVE: Regulated on activation, normal T-cell expressed and secreted (RANTES)/chemokine(C-C motif) ligand (CCL5) is expressed by adipocytes, and serum levels of RANTES are increased in obesity and type 2 diabetes. The aim of this study was to test the hypothesis that RANTES is involved in the pathogenesis of type 2 diabetes by analyzing the triangular association between CCL5 gene polymorphisms, systemic RANTES concentrations, and incident type 2 diabetes in a large prospective study. SUBJECTS AND METHODS: The study is based on 502 individuals (293 men and 209 women) and 1632 individuals (859 men and 773 women) with and without incident type 2 diabetes from the population-based MONItoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) case-cohort study respectively (mean follow-up time+/-s.d. 10.1+/-4.9 years). CCL5 genotypes and RANTES serum concentrations were determined and associations between genotypes, haplotypes, serum levels, and incident type 2 diabetes were assessed. Results Minor alleles of four single nucleotide polymorphisms were associated with lower RANTES levels (P(additive) between 1.2 x 10(-9) and 3.1 x 10(-8)), but neither genotypes, haplotypes, nor serum levels were associated with incident type 2 diabetes. CONCLUSIONS: Our data suggest that RANTES/CCL5 gene variants and serum levels are not causally related with type 2 diabetes and that elevated RANTES levels in patients with type 2 diabetes may be a consequence of hyperglycemia. However, our findings cannot preclude a local role in adipose tissue where RANTES expression may contribute to leukocyte infiltration and a proinflammatory state.
Authors: Mohamad M Adada; K Alexa Orr-Gandy; Ashley J Snider; Daniel Canals; Yusuf A Hannun; Lina M Obeid; Christopher J Clarke Journal: J Biol Chem Date: 2013-08-09 Impact factor: 5.157
Authors: Christian Herder; Jens Baumert; Astrid Zierer; Michael Roden; Christa Meisinger; Mahir Karakas; Lloyd Chambless; Wolfgang Rathmann; Annette Peters; Wolfgang Koenig; Barbara Thorand Journal: PLoS One Date: 2011-06-06 Impact factor: 3.240
Authors: Christian Herder; Wouter Peeters; Thomas Illig; Jens Baumert; Dominique P V de Kleijn; Frans L Moll; Ulrike Poschen; Norman Klopp; Martina Müller-Nurasyid; Michael Roden; Michael Preuss; Mahir Karakas; Christa Meisinger; Barbara Thorand; Gerard Pasterkamp; Wolfgang Koenig; Themistocles L Assimes; Panos Deloukas; Jeanette Erdmann; Hilma Holm; Sekar Kathiresan; Inke R König; Ruth McPherson; Muredach P Reilly; Robert Roberts; Nilesh J Samani; Heribert Schunkert; Alexandre F R Stewart Journal: PLoS One Date: 2011-12-06 Impact factor: 3.240
Authors: John R B Perry; Michael N Weedon; Claudia Langenberg; Anne U Jackson; Valeriya Lyssenko; Thomas Sparsø; Gudmar Thorleifsson; Harald Grallert; Luigi Ferrucci; Marcello Maggio; Giuseppe Paolisso; Mark Walker; Colin N A Palmer; Felicity Payne; Elizabeth Young; Christian Herder; Narisu Narisu; Mario A Morken; Lori L Bonnycastle; Katharine R Owen; Beverley Shields; Beatrice Knight; Amanda Bennett; Christopher J Groves; Aimo Ruokonen; Marjo Riitta Jarvelin; Ewan Pearson; Laura Pascoe; Ele Ferrannini; Stefan R Bornstein; Heather M Stringham; Laura J Scott; Johanna Kuusisto; Peter Nilsson; Malin Neptin; Anette P Gjesing; Charlotta Pisinger; Torsten Lauritzen; Annelli Sandbaek; Mike Sampson; Ele Zeggini; Cecilia M Lindgren; Valgerdur Steinthorsdottir; Unnur Thorsteinsdottir; Torben Hansen; Peter Schwarz; Thomas Illig; Markku Laakso; Kari Stefansson; Andrew D Morris; Leif Groop; Oluf Pedersen; Michael Boehnke; Inês Barroso; Nicholas J Wareham; Andrew T Hattersley; Mark I McCarthy; Timothy M Frayling Journal: Hum Mol Genet Date: 2009-11-18 Impact factor: 6.150
Authors: V D'Esposito; F Passaretti; A Hammarstedt; D Liguoro; D Terracciano; G Molea; L Canta; C Miele; U Smith; F Beguinot; P Formisano Journal: Diabetologia Date: 2012-07-15 Impact factor: 10.122