RANTES/CCL5 gene polymorphisms, serum concentrations, and incident type 2 diabetes: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.
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.


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.
Herder
Christian
C
Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich Heine University, 40225 Düsseldorf, Germany.
Illig
Thomas
T
Baumert
Jens
J
Müller
Martina
M
Klopp
Norman
N
Khuseyinova
Natalie
N
Meisinger
Christa
C
Poschen
Ulrike
U
Martin
Stephan
S
Koenig
Wolfgang
W
Thorand
Barbara
B
D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
C483024:CCL5 protein, human; D018946:Chemokine CCL5