Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early-onset coronary artery disease in patients with no classic risk factors.
OBJECTIVE
CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand.


METHODS
We examined the frequencies of V249I and T280M among early-onset CAD patients (G1; n = 149; <50 years), late-onset CAD patients (G2; n = 150; >65 years) and healthy controls (HC; n = 149, 47-93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein-C (HDL-C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non-carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI).


RESULTS
G1 patients had non-significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL-C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related.


CONCLUSIONS
There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early-onset CAD. Neither allele affected MI or lipid levels.
Nassar
B A
BA
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada. bassam.nassar@cdha.nshealth.ca
Nanji
A A
AA
Ransom
T P
TP
Rockwood
K
K
Kirkland
S A
SA
Macpherson
K
K
Connelly
P W
PW
Johnstone
D E
DE
O'Neill
B J
BJ
Bata
I R
IR
Andreou
P
P
Title
L M
LM
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D000073883:CX3C Chemokine Receptor 1; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D000073883:CX3C Chemokine Receptor 1; D008075:Lipoproteins, HDL; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D002784:Cholesterol