BACKGROUND AND PURPOSE: Migraine is a genetically heterogeneous disorder that is frequently associated with a familial history, and mitochondrial dysfunction has been suggested to be associated with its pathogenesis. We screened and scanned mitochondrial gene polymorphisms to determine the significance of mitochondrial DNA mutations in Korean migraineurs. METHODS: One hundred and sixty-four migraineurs aged 33.9+/-11.7 years (mean+/-SD range 12 to 65 years) were studied. Clinical data of the familial history were obtained, and blood samples were collected for DNA purification. An A-to-G substitution at mitochondrial DNA (mtDNA) position 11,084 (A11084G) was determined by a polymerase chain reaction (PCR) with BsmI restriction. In addition, new single-nucleotide polymorphism (SNP) sites in the mitochondrial genome were scanned for using PCR and direct sequencing. RESULTS: Ninety-eight migraine patients (59.8%) had a maternal familial history. The A11084G polymorphism, which was previously reported in 25% of Japanese migraineurs, was not evident in our Korean migraine patients. However, scanning of new SNP sites in mtDNA revealed six candidate SNPs whose incidences were higher in migraine patients than in normal subjects. CONCLUSIONS: Our study found no association between the A11084G polymorphism in mitochondrial DNA and migraine in Koreans. However, we found potential new mitochondrial SNP sites in Korean migraineurs, which warrant further investigation.
Asian Continental Ancestry Group ; DNA ; DNA, Mitochondrial ; Genes, Mitochondrial ; Genome, Mitochondrial* ; Humans ; Incidence ; Mass Screening* ; Migraine Disorders ; Mitochondria ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been implicated in both migraine and ischemic stroke. The homozygous C677T mutation in the MTHFR gene was more frequent in the Japanese and Turkish migraineurs than in the control group. Positive associations have also been found in ischemic stroke. The purpose of this study is to investigate the role of MTHFR C677T polymorphism in Korean patients with migraine or ischemic stroke. METHODS: We analyzed the allele frequencies and genotype of MTHFR C677T polymorphism in 115 patients with migraine, 213 with cerebral infarction, and 73 controls. RESULTS: There was no significantly increased frequency of homozygosity for the T677 allele in both of the diagnostic groups, compared to the controls. CONCLUSIONS: Our results suggest that MTHFR gene C677T polymorphism is unlikely to play a major role in the pathogenesis of migraine or ischemic stroke in Korean patients.
Alleles ; Asian Continental Ancestry Group ; Cerebral Infarction ; Gene Frequency ; Genotype ; Homocysteine ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Migraine Disorders* ; Stroke*

Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)100] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immnuocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)18] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome- lysosomal accumulation, from a 'dispersed vacuole (DV)' type into a coalescent 'perinuclear vacuole (PV)' type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome-lysosomal system, and that this contributes to huntingtin proteolysis.
Peptide Hydrolases/metabolism ; Nuclear Proteins/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; NIH 3T3 Cells ; Mice ; Lysosomes/*metabolism ; HSP70 Heat-Shock Proteins/genetics/*metabolism ; Endosomes/*metabolism ; Cytoplasm/metabolism ; Cell Survival ; Animals