An investigation of genetic risk factors for migraine
Migraine manifests itself episodically with incidence ranging from one attack in a lifetime to one almost every day. Most migraineurs suffer from typical migraine with or without aura, that is inherited in a complex manner. A small number of migraineurs suffer from FHM, a condition that exhibits Mendelian inheritance. BFNC is another rare episodic disorder that exhibits Mendelian inheritance. In a four generational family the BFNC phenotype was linked to the KCNQ2 gene on chromosome 20q13.3. Blood samples and epidemiological information were collected from 214 migraine probands in the Grampian region. An Access database was created to hold these data which were subsequently input. The database was utilised to extract epidemiological information about the cohort for subsequent analysis. These data were compared to other studies to characterise the severity of the cohort. A total of six polymorphisms were analysed by association analysis for involvement in migraine. The first polymorphism to be analysed was the -141C Ins/Del polymorphism in the DRD2 gene on chromosome 11q22. This polymorphism was analysed by restriction digest. Statistical analysis excluded this polymorphism and the regions encompassed by linkage disequilibrium in the aetiology of migraine. The second and third polymorphisms were located in intron 1 of the ERa gene on chromosome 6q25. These two polymorphisms were identified by restriction digest. Individual and haplotype analysis excluded the involvement of both polymorphisms in the aetiology of migraine. The fourth, fifth and sixth polymorphisms were located in exon 47, exon 23 and exon 8 of the CACNA1A gene on chromosome 19p13. The polymorphisms were analysed by capillary electrophoresis, restriction digest and DASH, respectively. All three polymorphisms were excluded from the aetiology of migraine. A total of 12 hot spot exons were sequenced in the CACNA1A gene in one individual afflicted by FHM and two by HM. No mutations were presented in the exons sequenced.