The genetic variation of the tenomodulin gene (TNMD) is associated with serum levels of systemic immune mediators--the Finnish Diabetes Prevention Study.
OBJECTIVE
We have reported that the genetic variation of the tenomodulin gene (TNMD) is associated with the risk of type 2 diabetes (T2DM), central obesity, and impaired glucose metabolism and the TNMD mRNA levels correlate with serum and mRNA levels of inflammatory markers. Our objective was to investigate the genetic associations of the single nucleotide polymorphisms of the TNMD gene with the serum levels of systemic immune mediators.


METHODS
Seven single nucleotide polymorphisms were genotyped from 507 participants of the Finnish Diabetes Prevention Study. All subjects had body mass index >25 and impaired glucose tolerance.


RESULTS
The sequence variation of tenomodulin was consistently associated with the serum concentrations of acute phase reactants, macrophage migration inhibitory factor, and CCR5 receptor ligands. The genotype effects were modified by status of glucose metabolism and central obesity. Markers associated with increased risk of T2DM in our previous study were associated with serum concentrations of acute phase proteins in men so that the subjects possessing the genotypes associated with increased risk of T2DM had higher serum concentrations of acute phase reactants.


CONCLUSIONS
These results indicate that the genetic variation of TNMD is associated with low-grade inflammation. The putative link between TNMD and T2DM could be mediated through the effects on systemic immune mediators.
Tolppanen
Anna-Maija
AM
Department of Clinical Nutrition and Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland. anna-maija.tolppanen@uku.fi
Pulkkinen
Leena
L
Herder
Christian
C
Koenig
Wolfgang
W
Kolehmainen
Marjukka
M
Lindström
Jaana
J
Tuomilehto
Jaakko
J
Uusitupa
Matti
M
D000209:Acute-Phase Proteins / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005387:Finland; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood; D015810:Linkage Disequilibrium; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019713:Receptors, CCR5 / Q000097:blood
D000209:Acute-Phase Proteins; D008263:Macrophage Migration-Inhibitory Factors; D008565:Membrane Proteins; D019713:Receptors, CCR5; C422444:TNMD protein, human; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human