Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients.
ABSTRACT: In this study, we investigated the association of migraine with the Variable Number of Tandem Repeats (VNTR), repeated as 27 base pair, gene polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) and the insertion/deletion of angiotensin converting enzyme (ACE) gene polymorphisms.One hundred and five migraine and ninety seven healthy female control subjects were enrolled in the study. The patients were subdivided as migraine with aura and without aura, and the frequency and severity of migraine headaches were recorded. The eNOS VNTR (eNOS 4 a/b) and ACE insertion/deletion gene polymorphisms (ACE I/D) were assessed by polymerase chain reactions.The allele and genotype frequencies of eNOS 4 a/b gene polymorphism showed no difference between the migraine and control groups. The genotypic distribution of the ACE I/D gene polymorphism in the migraine group significantly differed from that in the control group. The DD and ID genotype increased the risk of migraine as much as 2.571 (95% CI-1.138-5.811) and 4.453 (95% CI-2.006-9.883) compared to the II genotype. The same increased risk sustained for both genotypes in the migraine with aura subgroup, but only the ID genotype remained as the risk factor in the migraine without aura subgroup (OR-3.750, 95% CI-1.493-9.420). No association of gene polymorphisms with migraine frequency and severity was observed.Our findings support the relationship between migraine and the ACE I/D gene polymorphism. However, no association was found between migraine and the eNOS 4 a/b gene polymorphism.
Project description:BACKGROUND:Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial. METHODS:Association study among 25,000 white US women, participating in the Women's Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD. RESULTS:At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22-3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52-3.51; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke. CONCLUSIONS:Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.
Project description:Data on the association between the MTHFR 677C>T and ACE D/I polymorphisms and migraine including aura status are conflicting.The objective of this study is to perform a systematic review and meta-analysis on this topic.We searched for studies published until March 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies and reviews on the topic. Assessment for eligibility of studies and extraction of data was performed by 2 independent investigators. For each study we calculated the odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs.Thirteen studies investigated the association between the MTHFR 677C>T polymorphism and migraine. The TT genotype was associated with an increased risk for any migraine, which only appeared for migraine with aura (pooled OR = 1.48, 95% CI 1.02-2.13), but not for migraine without aura. Nine studies investigated the association of the ACE D/I polymorphism with migraine. The II genotype was associated with a reduced risk for migraine with aura (pooled OR = 0.71, 95% CI 0.55-0.93) and migraine without aura (pooled OR = 0.84, 95% CI 0.70-0.99). Results for both variants were driven by studies in non-Caucasian populations. Results among Caucasians did not suggest an association. Extractable data did not allow investigation of gene-gene interactions.The MTHFR 677TT genotype is associated with an increased risk for migraine with aura, while the ACE II genotype is protective against both migraine with and without aura. Results for both variants appeared only among non-Caucasian populations. There was no association among Caucasians.
Project description:INTRODUCTION:Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. MATERIALS AND METHODS:The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). RESULTS:Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. CONCLUSION:We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.
Project description:Data on the association of the MTHFR 677C→T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 ≥ weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 ≥ weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.
Project description:We investigated the phenotype-genotype association of the following endothelial nitric oxide synthase (eNOS) gene polymorphisms, rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851, in patients suffering from migraine living in Edirne, Turkey. A total of 175 individuals, who had been diagnosed with migraine between April 2013 and December 2013, at the Neurology Department, Trakya University Medical Faculty, Edirne, Turkey, and 125 healthy controls were recruited. The above gene polymorphisms were analyzed from genomic DNA in both patient and control groups, using the pyro-sequencing method. The eNOS rs1799983 TT genotype frequency in migraine patients who had a headache duration of longer than 24 hours was statistically significantly higher than in patients who had migraine attacks that lasted under 24 hours (p = 0.047). In terms of the AGGTGGA haplotype, the severity of headache was statistically significant, and was found to be severe in 61.0% (p = 0.0001). Also in terms of the AGGTGGA haplotype, the duration of headache was statistically significant, and was >24 hours in 56.0% of patients (p = 0.008). In our study, there was no significant genotypephenotype relationship between eNOS rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851 gene polymorphisms and migraine patients with and without aura living in Edirne, Turkey. The AGGTGGA haplotype constitutes a risk in terms of the severity and the duration of headaches in patients with migraine. This risk is significantly higher in patients with migraine with aura than patients with migraine without aura.
Project description:Interrelationships among the MTHFR 677C>T polymorphism (rs1801133), migraine, and cardiovascular disease (CVD) are plausible but remain controversial.Association study among 25,001 white US women, participating in the Women's Health Study, with information on MTHFR 677C>T polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationships of genotype and migraine on incident CVD.At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 CVD events occurred. Carriers of the TT genotype were less likely to have migraine with aura. The multivariable-adjusted relative risk (RR) in the recessive model was 0.79 (95% CI = 0.65-0.96; p = 0.02). The TT genotype did not increase the risk for CVD. In contrast, migraine with aura doubled the risk for CVD (multivariable-adjusted RR = 2.06; 95% CI = 1.53-2.78; p < 0.0001). Coexistence of migraine with aura and the TT genotype selectively raised this risk (RR = 3.66; 95% CI = 1.69-7.90; p = 0.001). This pattern was driven by a fourfold increased risk for ischemic stroke (multivariable-adjusted RR = 4.19; 95% CI = 1.38-12.74; p = 0.01) and was not apparent for myocardial infarction.Data from this large cohort of women suggest a modest protective effect of the MTHFR 677TT genotype on migraine with aura. The increased risk for cardiovascular disease among migraineurs with aura was magnified for TT genotype carriers, which was driven by a substantially increased risk of ischemic stroke.
Project description:Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution-rs2234694) and SOD2 gene (C/T transition-rs4880-Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering.
Project description:BACKGROUND AND PURPOSE:Five single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population. METHODS:This was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction-restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients. RESULTS:The frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05). CONCLUSIONS:Our findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.
Project description:Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2) polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group]) were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS) and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.
Project description:Data on the association between the SLC6A4 5-HTTLPR polymorphism and migraine are conflicting. We performed a systematic review and meta-analysis among studies published up to September 2009. For each study with genotype information, we calculated odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs.Among the ten studies identified there was no overall association between the polymorphism and any migraine for Europeans or Asians. However, European women carrying the S allele had an increased risk for any migraine (dominant model: pooled OR=2.02; 95% CI 1.24-3.28). Results among Europeans further suggested an increased risk for migraine with aura among carriers of the S/S genotype (recessive model: pooled OR=1.41; 95% CI 0.83-2.40).While our results indicate no overall association between the SLC6A4 5-HTTLPR polymorphism and migraine among Europeans and Asians, gender and migraine aura status may have modifying roles among Europeans.