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SHR Neuro Cancer Cardio Lipid Metab Microb
Benke, K; Ágg, B; Mátyás, G; Szokolai, V; Harsányi, G; Szilveszter, B; Odler, B; Pólos, M; Maurovich-Horvat, P; Radovits, T; Merkely, B; Nagy, ZB; Szabolcs, Z.
Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome. Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome.
Thromb Haemost. 2015; 114(4): 748-756.
Doi: 10.1160/TH15-02-0096
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- Odler Balazs
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- Abstract:
- Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta.
- Find related publications in this database (using NLM MeSH Indexing)
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - metabolism
- Adolescent -
- Adult -
- Aneurysm, Dissecting - diagnosis
- Aneurysm, Dissecting - enzymology
- Aneurysm, Dissecting - genetics
- Aneurysm, Dissecting - therapy
- Aortic Aneurysm - blood
- Aortic Aneurysm - diagnosis
- Aortic Aneurysm - enzymology
- Aortic Aneurysm - genetics
- Aortic Aneurysm - therapy
- Biomarkers - blood
- Case-Control Studies -
- Chi-Square Distribution -
- Female -
- Ferredoxin-NADP Reductase - genetics
- Ferredoxin-NADP Reductase - metabolism
- Folic Acid - blood
- Gene Frequency -
- Genetic Association Studies -
- Genetic Predisposition to Disease -
- Heterozygote -
- Homocysteine - blood
- Homozygote -
- Humans -
- Logistic Models -
- Male -
- Marfan Syndrome - blood
- Marfan Syndrome - complications
- Marfan Syndrome - diagnosis
- Marfan Syndrome - enzymology
- Marfan Syndrome - genetics
- Methylenetetrahydrofolate Reductase (NADPH2) - genetics
- Methylenetetrahydrofolate Reductase (NADPH2) - metabolism
- Middle Aged -
- Multivariate Analysis -
- Odds Ratio -
- Phenotype -
- Polymorphism, Single Nucleotide -
- Predictive Value of Tests -
- Risk Factors -
- Severity of Illness Index -
- Up-Regulation -
- Vitamin B 12 - blood
- Young Adult -
- Find related publications in this database (Keywords)
- Cardiology
- vascular remodelling
- single nucleotide polymorphism
- HCY
- matrix-metalloproteinases