angiotensinogen and Migraine-Disorders

CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype.. Altogether, 134 Finnish CADASIL patients with p.Arg133Cys mutation were analysed for possible associations between the apolipoprotein E (APOE) genotype, angiotensinogen (AGT) p.Met268Thr polymorphism or neutral p.Ala202Ala NOTCH3 polymorphism and earlier first-ever stroke or migraine.. We found no association between the APOE genotypes, AGT polymorphism, NOTCH3 polymorphism and earlier first-ever stroke or migraine.. The APOE, AGT and NOTCH3 polymorphism did not modify the onset of strokes or migraine in our CADASIL sample, which is one of the largest mutationally homogenous CADASIL populations published to date. International collaboration, pooled analyses and genomewide approaches are warranted to identify the genetic factors that modify the highly variable CADASIL phenotype.

Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Angiotensinogen; Apolipoproteins E; CADASIL; Female; Finland; Gene Frequency; Humans; Male; Middle Aged; Migraine Disorders; Mutation; Phenotype; Polymorphism, Single Nucleotide; Receptor, Notch3; Receptors, Notch; Stroke; Young Adult

Recent findings suggest an association between the renin-angiotensin system and migraine. However, genetic studies are scarce and controversial.. To investigate the association between the AGTR1 1166A > C and AGT Met235Thr polymorphisms with migraine and migraine aura status.. We performed an association study among 25,000 Caucasian US women, participating in the Women's Health Study, with information on the AGTR1 1166A > C and AGT Met235Thr polymorphisms. Migraine and migraine aura status were self-reported. We distinguished between any history of migraine, active migraine with aura, active migraine without aura, and prior migraine (history of migraine, but not in the year prior to baseline). We used logistic regression to investigate the genotype-migraine association.. At baseline, 4577 (18.3%) women reported any history of migraine; 39.5% of the 3226 women with active migraine indicated aura. The polymorphisms were not associated with migraine or migraine-specific subgroups. We also did not find a significant interaction between the polymorphisms.. Data from this large cohort of Caucasian women do not suggest an association of polymorphisms in the renin-angiotensin system with migraine or aura status. Future studies should focus on haplotype analyses and additional gene-gene as well as gene-environment interactions.

Topics: Angiotensinogen; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Middle Aged; Migraine Disorders; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Receptors, Androgen; Renin-Angiotensin System