Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.
Eur J Vasc Endovasc Surg
; 35(1): 31-6, 2008 Jan.
Article
in En
| MEDLINE
| ID: mdl-17996468
ABSTRACT
BACKGROUND:
Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs.METHODS:
An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework.RESULTS:
IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI 1.02, 2.39).CONCLUSION:
The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-6
/
Promoter Regions, Genetic
/
Aortic Aneurysm, Abdominal
/
Polymorphism, Single Nucleotide
Type of study:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Humans
/
Male
Language:
En
Journal:
Eur J Vasc Endovasc Surg
Journal subject:
ANGIOLOGIA
Year:
2008
Document type:
Article