Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A-->G promoter polymorphism.
OBJECTIVE
To investigate the association of serum levels and the -2518 A-->G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus.


METHODS
MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients.


RESULTS
Two hundred and thirty-one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non-diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP-1 mean concentrations and percentiles were substantially higher in non-diabetic populations but were not influenced by the genotype (AA: 662.0 +/- 323.0 pg/ml; AG: 730.6 +/- 491.4 pg/ml; GG: 641.2 +/- 323.8 pg/ml). MCP-1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF-alpha and IL-6).


CONCLUSIONS
This is the first study providing MCP-1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP-1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non-diabetic patients and were not related to MCP-1 levels. The mechanisms behind these elevated MCP-1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes.
Zietz
B
B
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Büchler
C
C
Herfarth
H
H
Müller-Ladner
U
U
Spiegel
D
D
Schölmerich
J
J
Schäffler
A
A
D000368:Aged; D000886:Anthropometry; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D012737:Sex Factors; D044465:White People
D018932:Chemokine CCL2; D016207:Cytokines; D007328:Insulin; D020738:Leptin; D002784:Cholesterol