ABSTRACT
Title
Migraine and Coronary Artery Disease: an Open Study on the Genetic polymorphism of the 5, 10 methylenetetrahydrofolate (MTHFR) and angiotensin I-converting enzyme (ACE) genes
Authors
V. Pizza (1), A. Agresta (1), A. Bisogno (2), A. Capasso (2),
1) Neurophysiopatology, S. Luca Hospital, Vallo della Lucania (SA), 2) Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Italy.
1) Neurophysiopatology, S. Luca Hospital, Vallo della Lucania (SA), 2) Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Italy.
Abstract
The potential association between migraine and ischaemic stroke risk is an important public health concern, but the causal relationship between them is complex and not fully clear. Migraine and stroke can coexist, stroke may occur with the clinical features of migraine, or it may be induced by migraine. In the last case, a prolonged migraine aura may provoke a condition called “true migrainous infarction” (L.K. Mannix, 2005).There are good epidemiological proofs about the association of migraine not only with an increased risk of stroke (which is stronger in young adults, but may persist in the elderly) but also with any vascular ischaemic event, myocardial infarction included.
Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The “TT” polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors.
The aim of the our study is evaluate the incidence of ACE and MTHFR polymorphism in a consecutive series of migrainous patients and of patients affected by myocardial infarction.
We studied a series of 90 migrainous patients [1] aged 35.7 years +/- 16.2 (18 MWA and 72 MwA, ICHDII-2004 criteria) and of80 patients [2] affected by Acute Myocardial Infarction (AMI). The analyse was based on Polymerase Chain Reaction (PCR) and on reverse-hybridization.
MTHFR (C677T): 58 patients (64.4%) [1] and 47 (58.7%) [2] were heterozygous; 2 patients (2.2%) [1] and 5 (6.2%) [2] were mutated. MTHFR (A1298C): 47 patients (52.2%) [1] and 40 (50%) [2] were heterozygous, 8 patient (8.8%) [1] and 6 (7.5%) [2] were mutated. ACE: 36 patients (40%) [1] and 43 (53.7%) [2] had an ID genotype; 44 (48.8%) [1] and 31 (38.7%) [2] had a DD genotype.
The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.
L.K. Mannix: Comorbidities of migraine. Sponsored by the National Headache Foundation, 2005
R. A. Lea, M. Ovcaric, J. Sundholm, L. Solyom, J. MacMillan, LR Griffiths: Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. Brain Res Mol Brain Res., 136 (1-2): 112-7, 2005.
Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The “TT” polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors.
The aim of the our study is evaluate the incidence of ACE and MTHFR polymorphism in a consecutive series of migrainous patients and of patients affected by myocardial infarction.
We studied a series of 90 migrainous patients [1] aged 35.7 years +/- 16.2 (18 MWA and 72 MwA, ICHDII-2004 criteria) and of80 patients [2] affected by Acute Myocardial Infarction (AMI). The analyse was based on Polymerase Chain Reaction (PCR) and on reverse-hybridization.
MTHFR (C677T): 58 patients (64.4%) [1] and 47 (58.7%) [2] were heterozygous; 2 patients (2.2%) [1] and 5 (6.2%) [2] were mutated. MTHFR (A1298C): 47 patients (52.2%) [1] and 40 (50%) [2] were heterozygous, 8 patient (8.8%) [1] and 6 (7.5%) [2] were mutated. ACE: 36 patients (40%) [1] and 43 (53.7%) [2] had an ID genotype; 44 (48.8%) [1] and 31 (38.7%) [2] had a DD genotype.
The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.
L.K. Mannix: Comorbidities of migraine. Sponsored by the National Headache Foundation, 2005
R. A. Lea, M. Ovcaric, J. Sundholm, L. Solyom, J. MacMillan, LR Griffiths: Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. Brain Res Mol Brain Res., 136 (1-2): 112-7, 2005.