Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia.
OBJECTIVE
Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI.


METHODS
In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) - 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3-1171 5A/6A and MMP-9-1563 C/T.


RESULTS
We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual.


CONCLUSIONS
Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders.
Flex
A
A
Laboratory of Vascular Biology & Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
Gaetani
E
E
Angelini
F
F
Sabusco
A
A
Chillà
C
C
Straface
G
G
Biscetti
F
F
Pola
P
P
Castellot
J J
JJ
Pola
R
R
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007511:Ischemia / Q000235:genetics*; D007866:Leg / Q000098:blood supply*; D008297:Male; D016491:Peripheral Vascular Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
D018836:Inflammation Mediators