Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS).
BACKGROUND
CD40/CD40L signaling is known to play an important role in immune response. The proteins are expressed in a variety of cell types and ligation causes cells to produce inflammatory cytokines and cellular adhesion molecules. These processes are implicated in the development and progression of atherosclerosis. Animal models demonstrate that interruption of CD40/CD40L signaling produces a more fibrous and stable atherosclerotic lesion.


METHODS
We investigated the role of genetic variation in CD40 and CD40L genes in subclinical atherosclerosis assessed by coronary artery calcification (CAC) and carotid intima-media thickness in 620 individuals from 230 families in the DHS.


RESULTS
Two single nucleotide polymorphisms in the CD40 gene (rs1535045 and rs3765459) were significantly associated with decreased CAC (P < or = .02) in this population. CD40L single nucleotide polymorphisms were not significantly associated. In addition, no associations with carotid intima-media thickness, carotid artery calcification, or C-reactive protein levels were detected for either gene.


CONCLUSIONS
Genetic variation in the CD40 gene is associated with CAC in diabetic families.
Burdon
Kathryn P
KP
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Langefeld
Carl D
CD
Beck
Stephanie R
SR
Wagenknecht
Lynne E
LE
Carr
J Jeffrey
JJ
Rich
Stephen S
SS
Freedman
Barry I
BI
Herrington
David
D
Bowden
Donald W
DW
D002097:C-Reactive Protein / Q000032:analysis; D019013:CD40 Antigens / Q000235:genetics*; D023201:CD40 Ligand / Q000235:genetics*; D002118:Calcium / Q000032:analysis; D003324:Coronary Artery Disease / Q000235:genetics*; D003331:Coronary Vessels / Q000737:chemistry; D003925:Diabetic Angiopathies / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D019013:CD40 Antigens; D023201:CD40 Ligand; D002097:C-Reactive Protein; D002118:Calcium