PMC:3727988 / 1879-4912 JSONTXT

{"project":"2_test","denotations":[{"id":"23815568-22572707-60544988","span":{"begin":327,"end":328},"obj":"22572707"},{"id":"23815568-22162417-60544989","span":{"begin":540,"end":541},"obj":"22162417"},{"id":"23815568-22200764-60544990","span":{"begin":1168,"end":1169},"obj":"22200764"},{"id":"23815568-22030984-60544991","span":{"begin":1330,"end":1331},"obj":"22030984"},{"id":"23815568-22678113-60544992","span":{"begin":1797,"end":1798},"obj":"22678113"},{"id":"23815568-22666411-60544993","span":{"begin":2441,"end":2442},"obj":"22666411"},{"id":"23815568-22072275-60544994","span":{"begin":2443,"end":2444},"obj":"22072275"},{"id":"23815568-21448238-60544995","span":{"begin":2464,"end":2465},"obj":"21448238"},{"id":"23815568-22908361-60544996","span":{"begin":3026,"end":3028},"obj":"22908361"},{"id":"23815568-22103325-60544997","span":{"begin":3029,"end":3031},"obj":"22103325"}],"text":"In an effort to identify genetic variants involved in migraine risk and influencing the appropriate pharmacological treatments, many genomic studies have been performed in the last years. Due to neurological origin of migraine, some researchers have studied receptors involved in mediation of neuronal activities. Chen et al. [2] characterized one polymorphism in GABRG2 gene encoding the GABAA receptor gamma-2-subunit (rs211037) on a migraine case–control population of 546 subjects. No significant correlation was found. Carreno et al. [3] studied the transient receptor potential (TRP) superfamily of non-selective cationic channels accountable of multimodal sensory and pain perception, central and peripheral sensitization, and regulation of calcium homeostasis, relevant steps of migraine physiopathology. They carried out a migraine-control genetic association study genotyping 149 SNPs covering 14 TRP genes. Consistent results were obtained for TRPV3 rs7217270 in the Migraine with aura group and TRPV1 rs222741 in the overall migraine group, suggesting the involvement of the vanilloid TRPV subfamily of receptors to the genetic susceptibility to migraine [4]. Another gene analyzed is the calcium-activated potassium ion channel gene (KCNN3) involved in neural excitability and in migraine susceptibility. Cox et al. [5] performed a gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, characterized by high percentage of migraineurs. A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals. Only four intronic SNPs displayed gene-wide significance: rs4845663, rs7532286, rs6426929 and rs1218551, with the minor allele in each case conferring protection against migraine risk. Using the same population, Cox et al. [6] carried out another pedigree-based genome-wide association (GWA) study found a significant statistical association with SNP rs4807347 in ZNF555 gene, coding for a zing finger protein. This result has been confirmed in unrelated cohort with more than 500 patients affected by migraine. They also found 4 SNPs in neurotransmitter-related genes (ADARB2, GRM7 and HTR7 genes) suggesting an alteration in the serotoninergic pathway. Maher et al., characterized the entire X chromosome in an association study on the Norfolk population and provides evidence for the SNP rs102834 in the UTR of the HEPH gene, which is involved in iron homeostasis [7,8]. Ligthart et al. [9] performed a meta-analysis of GWA studies for migraine in six population-based European cohorts consisting of 2446 cases and 8534 controls. A total of 32 SNPs showed marginal evidence for association to migraine and the best result was obtained for SNP rs9908234 in the nerve growth factor receptor -NGFR- gene but those results were not replicated in other cohorts. Besides, they found a modest gene-based significant association between migraine and the rs1835740 near the metadherin gene, but further replication studies did not validated this association [10,11]."}