PMID- 17635597 OWN - NLM STAT- MEDLINE DCOM- 20070918 LR - 20090202 IS - 0017-8748 (Print) IS - 0017-8748 (Linking) VI - 47 IP - 7 DP - 2007 Jul-Aug TI - Association between a polymorphism in the lymphotoxin-a promoter region and migraine. PG - 1056-62 AB - OBJECTIVE: The aim of this study was to determine whether polymorphisms in the lymphotoxin (LTA)-tumor necrosis factor (TNF) region are associated with the risk of migraine. BACKGROUND: Previous studies concerning the role of TNFalpha in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFalpha polymorphism associated with migraine is in linkage disequilibrium with other functional polymorphisms that influence migraine risk. Moreover, there are significant differences among the allele frequencies of TNF gene variants among populations from different ethnic groups. METHODS: In a case-control study, including 439 migraine patients and 382 controls, we examined the association between 15 single nucleotide polymorphisms in the coding and promoter regions of LTA and TNFalpha genes, which are located within the 22 kb around TNF and the risk of migraine. We performed a chromatin immunoprecipitation (ChIP) assay and an electrophoretic mobility shift assay (EMSA) to identify differential protein-DNA binding of LTA-294. RESULTS: Homozygosity for the LTA-294C allele was significantly associated with an increased risk of migraine compared with CT/TT carriers (corrected P= .005, odds ratio [OR]= 1.7, 95% confidence interval [CI] 1.3-2.3). Haplotype TGAAC was found to be significantly associated with a protective effect against migraine (P= .0005, Bonferroni corrected P= .003, OR = 0.7, 95% CI 0.5-0.8). There was no differential protein-DNA binding pattern in both EMSA and ChIP assays. CONCLUSIONS: We found that the LTA haplotypes were associated with migraine among Koreans and that the best marker for this is the LTA-294 T/C polymorphism. Our results indicate that these associations should be defined in the context of the involvement of other genetically linked region, such as human leukocyte antigen (HLA) loci. FAU - Lee, Kyung-A AU - Lee KA AD - Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. FAU - Jang, Soo Yeon AU - Jang SY FAU - Sohn, Kwang-Min AU - Sohn KM FAU - Won, Hong Hee AU - Won HH FAU - Kim, Min Ji AU - Kim MJ FAU - Kim, Jong-Won AU - Kim JW FAU - Chung, Chin-Sang AU - Chung CS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Headache JT - Headache JID - 2985091R RN - 0 (Genetic Markers) RN - 0 (Lymphotoxin-alpha) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-49-2 (DNA) SB - IM MH - Adolescent MH - Adult MH - Aged MH - DNA/genetics/isolation & purification MH - Electrophoretic Mobility Shift Assay MH - Genetic Markers MH - Genotype MH - Humans MH - Lymphotoxin-alpha/blood/*genetics MH - Middle Aged MH - Migraine Disorders/blood/*genetics MH - *Polymorphism, Genetic MH - *Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic MH - Reference Values MH - Tumor Necrosis Factor-alpha/*genetics EDAT- 2007/07/20 09:00 MHDA- 2007/09/19 09:00 CRDT- 2007/07/20 09:00 PHST- 2007/07/20 09:00 [pubmed] PHST- 2007/09/19 09:00 [medline] PHST- 2007/07/20 09:00 [entrez] AID - HED847 [pii] AID - 10.1111/j.1526-4610.2007.00847.x [doi] PST - ppublish SO - Headache. 2007 Jul-Aug;47(7):1056-62. doi: 10.1111/j.1526-4610.2007.00847.x.