Interleukin-1 gene cluster variants and abdominal aortic aneurysms.
Inflammation is a key factor in the pathogenesis of abdominal aortic aneurysms (AAA). Interleukin 1 (IL-1), a fundamental regulator of the inflammatory cascade, has been shown to be involved in this process. Several functional polymorphisms in the IL-1 gene cluster are known. In this matched case-control study, we investigated a potential association between six genetic variants in IL-1 and IL-1 receptor antagonist (IL-1 RN) with AAA. We enrolled 405 individuals, 135 consecutive patients with AAA were individually age- and sex-matched to 270 patients with coronary artery disease (CAD). Traditional cardiovascular risk factors and IL-1 genotypes were determined, and the distribution of six single nucleotide polymorphisms were compared between patients and controls by multivariable conditional logistic regression analysis: IL-1A (-889) C>T, IL-1A (+4845) G>T, IL-1B (-511) C>T, IL-1B (-31) C>T, IL-1B (+3954) C>T and IL-1RN (+2018) C>T. IL-1A (-889) C>T and IL-1A (+4845) G>T (kappa 0.98,95% CI 0.96 to 1.00), and IL-1B (-511) C>T and IL-1B (-31) C>T (kappa 0.98, 95% CI 0.96 to 1.00) were closely linked, therefore IL-1A (-889) C>T and IL-1B (-31) C>T were not considered for further analyses. None of the 4 remaining polymorphisms showed a significant association with AAA: IL-1RN (+2018) C>T (p = 0.061), IL-1B (+3954) C>T (p = 0.51), IL-1B (-511) C>T (p = 0.61) and IL-1A (+4845) G>T (p = 0.81). No significant first-degree interactions between the genetic variants and AAA were detected. In conclusion,these six genetic variants in the interleukin- I gene cluster do not seem to play a clinically relevant role in the pathogenesis of AAA, although we cannot rule out the existence of higher degree gene-gene or gene-environment interactions.
Marculescu
Rodrig
R
Department of Medical and Chemical Laboratory Diagnostics, Vienna Medical University, Vienna, Austria.
Sodeck
Gottfried
G
Domanovits
Hans
H
Hobusch
Gerhard
G
Exner
Markus
M
Heinzl
Harald
H
Huber
Kurt
K
Mannhalter
Christine
C
Minar
Erich
E
Wagner
Oswald
O
Schillinger
Martin
M
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000235:genetics*; D001161:Arteriosclerosis / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins