Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm
- B Giusti1,
- C Saracini1,
- P Bolli2,
- A Magi1,
- I Sestini1,
- E Sticchi1,
- G Pratesi3,
- R Pulli4,
- C Pratesi4,
- R Abbate1
- 1Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, “DENOTHE”, University of Florence, Florence, Italy
- 2Centro S.Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy
- 3Vascular Surgery Unit, Department of Surgery, University of Rome “Tor Vergata”, Rome, Italy
- 4Department of Vascular Surgery, University of Florence, Florence, Italy
- Dr B Giusti, Department of Medical and Surgical Critical Care, University of Florence, Viale Morgagni 85, 50134 Florence, Italy; betti.giusti{at}unifi.it
- Received 18 January 2008
- Revised 5 June 2008
- Accepted 17 June 2008
- Published Online First 17 July 2008
Abstract
Background: Previous studies suggested an association between abdominal aortic aneurysm (AAA) and hyperhomocysteinaemia, a complex trait determined by genetic and environmental factors. Our hypothesis was that polymorphisms in genes directly or indirectly involved in methionine metabolism may contribute to AAA susceptibility.
Method: We studied 56 polymorphisms in MTHFR, MTR, MTRR, CBS, MTHFD1, SLC19A1, NNMT, TCN2, AHCY, BHMT, BHMT2, FOLH1, TYMS, ENOSF1, SHMT1, PON1, PON2 genes according to their demonstrated/putative function, localisation in promoter or regulatory and coding regions and/or heterozygosity values >0.300. Polymorphisms were evaluated by using a primer extension based microarray technology in 423 AAA patients and 423 matched controls.
Results: All polymorphisms resulted in Hardy–Weinberg equilibrium in patients and controls. At the multiple logistic regression analysis adjusted for traditional cardiovascular risk factors (sex, age, hypertension, smoking habit, dyslipidaemia, diabetes) and chronic obstructive pulmonary disease (COPD), rs8003379 MTHFD1 (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.26 to 0.65) and rs326118 MTRR (OR 0.47, 95% CI 0.29 to 0.77) polymorphisms resulted in independent susceptibility factor for AAA.
Conclusions: After haplotype reconstruction, logistic regression analyses adjusted for traditional risk factors and COPD showed a significant association among AAA and AHCY, FOLH1, MTHFD1, MTR, NNMT, PON1 and TYMS haplotypes. Our findings offer new insights into the pathogenesis of AAA.
Footnotes
-
Competing interests: None declared.
-
Funding: This work was supported by grants from “Genopolis” government FIRB project (RBLA038RMA_008) and from the Ente Cassa di Risparmio di Firenze to Fiorgen Foundation, Florence, Italy
-
Patient consent: Obtained
