PMID- 24708359 OWN - NLM STAT- MEDLINE DCOM- 20150604 LR - 20180816 IS - 1526-4610 (Electronic) IS - 0017-8748 (Linking) VI - 54 IP - 7 DP - 2014 Jul-Aug TI - Investigation of brain-derived neurotrophic factor (BDNF) gene variants in migraine. PG - 1184-93 LID - 10.1111/head.12351 [doi] AB - OBJECTIVE: A number of observations have suggested that brain-derived neurotrophic factor (BDNF) plays a role in migraine pathophysiology. This study investigates whether variants in the BDNF gene are associated with migraine in an Australian case-control population. BACKGROUND: BDNF has an important role in neural growth, development, and survival in the central nervous system and is an important modulator of central and peripheral pain responses. Variants in BDNF, in particular the functional Val66Met polymorphism (rs6265), have been found to be associated with a number of psychiatric disorders, cognitive function, and obesity. As BDNF has been found to be differentially expressed in a number of aspects related to migraine, we tested for association between single nucleotide polymorphisms (SNPs) in BDNF and migraine. METHODS: Five SNPs in the BDNF locus (rs1519480, rs6265, rs712507, rs2049046, and rs12273363) were genotyped initially in a cohort of 277 migraine cases, including 172 diagnosed with migraine with aura (MA) and 105 with migraine without aura (MO), and 277 age- and sex-matched controls. Three of these SNPs (rs6265, rs2049046, and rs12273363) were subsequently genotyped in a second cohort of 580 migraineurs, including 473 diagnosed with MA and 105 with MO, and 580 matched controls. RESULTS: BDNF SNPs rs1519480, rs6265, rs712507, and rs12273363 were not significantly associated with migraine. However, rs2049046 showed a significant association with migraine, and in particular, MA in the first cohort. In the second cohort, although an increase in the rs2049046 T-allele frequency was observed in migraine cases, and in both MA and MO subgroups, it was not significantly different from controls. Analysis of data combined from both cohorts for rs2049046 showed significant differences in the genotypic and allelic distributions for this marker in both migraine and the MA subgroup. CONCLUSION: This study confirmed previous studies that the functional BDNF SNP rs6265 (Val66Met) is not associated with migraine. However, we found that rs2049046, which resides at the 5' end of one the BDNF transcripts, may be associated with migraine, suggesting that further investigations of this SNP may be warranted. CI - (c) 2014 American Headache Society. FAU - Sutherland, Heidi G AU - Sutherland HG AD - Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia. FAU - Maher, Bridget H AU - Maher BH FAU - Rodriguez-Acevedo, Astrid J AU - Rodriguez-Acevedo AJ FAU - Haupt, Larisa M AU - Haupt LM FAU - Griffiths, Lyn R AU - Griffiths LR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140407 PL - United States TA - Headache JT - Headache JID - 2985091R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Australia MH - Brain-Derived Neurotrophic Factor/*genetics MH - Case-Control Studies MH - Female MH - Genetic Predisposition to Disease/*genetics MH - Genetic Variation MH - Genotype MH - Humans MH - Male MH - Migraine Disorders/*genetics MH - Polymorphism, Restriction Fragment Length MH - Polymorphism, Single Nucleotide MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - BDNF OT - SNP OT - association study OT - migraine EDAT- 2014/04/09 06:00 MHDA- 2015/06/05 06:00 CRDT- 2014/04/09 06:00 PHST- 2014/02/17 00:00 [accepted] PHST- 2014/04/09 06:00 [entrez] PHST- 2014/04/09 06:00 [pubmed] PHST- 2015/06/05 06:00 [medline] AID - 10.1111/head.12351 [doi] PST - ppublish SO - Headache. 2014 Jul-Aug;54(7):1184-93. doi: 10.1111/head.12351. Epub 2014 Apr 7.