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

Abstract

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 our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, according to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1 patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45 patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (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.

Migraine and risk of stroke in older adults

“…24 Molecular genetics has revealed associations between migraine and genetic polymorphisms of angiotensin I-converting and enzyme, 5, 10 methylenetetrahydrofolate (MTHFR), suggesting the potential of shared genetic risks for stroke. 25 Further research may reveal subtypes of migraine, often with aura, at risk for stroke and vascular complications. 26 The mechanisms explaining why migraine was associated with vascular events only in smokers in our population are unclear.…”

Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis

“…Seven meeting abstracts were excluded because they did not provide detailed genotype or allele frequencies. Four studies with a case-case clinical design were excluded because they did not include healthy controls [26][27][28][29].…”

Migraine genetics: current findings and future lines of research

“…Association studies of genes involved in blood pressure regulation, endothelial cell function, vasoconstriction, and vasodilation have provided more consistent positive results (Table 4) [91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][122][123][124][125][126][127][128][129]. Many vascular genes associated with migraine also confer risk for stroke and heart disease [125][126][127]. This is especially important for MA, which displays a significant comorbidity with stroke and depression [15,16].…”