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British Journal of Surgery
Article . 2005 . Peer-reviewed
License: OUP Standard Publication Reuse
Data sources: Crossref
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Genotype–phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion

Authors: P, Eriksson; S, Jormsjö-Pettersson; A R, Brady; H, Deguchi; A, Hamsten; J T, Powell;

Genotype–phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion

Abstract

Abstract Background The aim of the study was to investigate the effect of functional polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP-12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small abdominal aortic aneurysms (AAA). Methods Some 455 individuals with a small AAA (4·0–5·5 cm) were monitored for aneurysm growth by ultrasonography (mean follow-up 2·6 years). They also provided a DNA sample for analysis of the −1306 C > T, −1171 5A > 6A, −1562 C > T, −82 A > G and −675 4G > 5G alleles of MMP-2, MMP-3, MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were calculated by flexible modelling; the sample size was sufficient to detect variants that influenced the growth rate by 25 per cent. Results For MMP-2, MMP-9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate of 3·08 mm per year. For MMP-3, growth rates were 3·05 (for 5A5A), 3·19 (for 5A6A) and 2·90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and 5G5G genotypes had growth rates of 3·18, 2·92 and 3·47 mm per year, respectively, for aneurysms with a baseline diameter of 45·1, 44·6 and 46·2 mm. The increased growth rate for patients with PAI-1 5G5G genotype was not statistically significant (P = 0·061), although these patients had the lowest plasma PAI-1 concentrations (P = 0·018). Conclusion There was no evidence that any specific MMP polymorphism had a clinically significant effect on AAA expansion. The plasminogen system may have a small but clinically significant role in AAA development. Much larger studies would be needed to evaluate genes of smaller effect.

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Keywords

Male, Analysis of Variance, Polymorphism, Genetic, Genotype, Middle Aged, Matrix Metalloproteinases, Phenotype, Gene Frequency, Plasminogen Activator Inhibitor 1, Humans, Female, Promoter Regions, Genetic, Aged, Aortic Aneurysm, Abdominal

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
27
Average
Top 10%
Top 10%
hybrid