GENETIC ANALYSIS OF 56 POLYMORPHISMS IN 18 GENES INVOLVED IN HOMOCYSTEINE METABOLISM IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSM
Abstract number: P-S-456
Giusti1 B., Saracini1 C., Bolli2 P., Sestini1 I., Sticchi2 E., Magi1 A., Pratesi3 G., Pulli3 R., Pratesi3 C., Abbate1 R.
11Department of Medical and Surgical Critical Care, University of Florence 22S.Maria agli Ulivi Center, Don C. Gnocchi Foundation Onlus IRCCS 33Department of Vascular Surgery, University of Florence, Florence, Italy
How-to-cite Giusti B, Saracini C, Bolli P, Sestini I, Sticchi E, Magi A, Pratesi G, Pulli R, Pratesi C, Abbate R. GENETIC ANALYSIS OF 56 POLYMORPHISMS IN 18 GENES INVOLVED IN HOMOCYSTEINE METABOLISM IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSM. J Thromb Haemost 2007; 5 Supplement 2: P-S-456
Abstract
Introduction: Previous studies have suggested an association between abdominal aortic aneurysm (AAA) and hyperhomocysteinemia, a complex trait determined by environmental and genetic factors. Our hypothesis was that genetic variations in genes directly or indirectly involved in methionine metabolism may contribute to susceptibility for AAA.
Methods: We selected 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 or putative function on the bases of literature data, localization in the promoter or regulatory region or exons and/or heterozygosity values>0.3. On genomic DNA of 390 patients and 390 sex and age matched controls we evaluated the 56 polymorphisms by using a microarray technology (GenomeLab SNP Stream Technology, Beckman Coulter).
Results: All of the polymorphisms resulted in Hardy-Weinberg equilibrium in AAA patients and controls. The genotype distribution of polymorphisms significantly differed in patients and controls for the following polymorphisms: rs8003379 MTHFD1, rs2853523 MTR, rs326118 MTRR, rs854660 PON1, rs8423 TYMS. After haplotype reconstruction, logistic regression analyses adjusted for traditional risk factors (sex, age, hypertension, smoking habit, dyslipidemia, diabetes) showed a significant association among AAA and FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1 and TYMS haplotypes.
Conclusions: This study identifies significant genetic associations between haplotypes in FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1 and TYMS genes, and AAA. If these data will be validated the evaluation of these genetic factors in combination with others could be used to identify individuals who are at increased risk for developing AAA.
