Association between a polymorphism in the lymphotoxin-a promoter region and migraine

Kyung A. Lee, Soo Yeon Jang, Kwang Min Sohn, Hong Hee Won, Min Ji Kim, Jong Won Kim, Chin Sang Chung

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 TNFα in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFα 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 TNFα 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.

Original languageEnglish
Pages (from-to)1056-1062
Number of pages7
JournalHeadache
Volume47
Issue number7
DOIs
Publication statusPublished - 2007 Jul 1

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Lymphotoxin-alpha
Migraine Disorders
Genetic Promoter Regions
Tumor Necrosis Factor-alpha
Chromatin Immunoprecipitation
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Haplotypes
Odds Ratio
Confidence Intervals
Genes
Linkage Disequilibrium
HLA Antigens
Ethnic Groups
Gene Frequency
Single Nucleotide Polymorphism
Case-Control Studies
Alleles

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Lee, K. A., Jang, S. Y., Sohn, K. M., Won, H. H., Kim, M. J., Kim, J. W., & Chung, C. S. (2007). Association between a polymorphism in the lymphotoxin-a promoter region and migraine. Headache, 47(7), 1056-1062. https://doi.org/10.1111/j.1526-4610.2007.00847.x
Lee, Kyung A. ; Jang, Soo Yeon ; Sohn, Kwang Min ; Won, Hong Hee ; Kim, Min Ji ; Kim, Jong Won ; Chung, Chin Sang. / Association between a polymorphism in the lymphotoxin-a promoter region and migraine. In: Headache. 2007 ; Vol. 47, No. 7. pp. 1056-1062.
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abstract = "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 TNFα in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFα 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 TNFα 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.",
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Lee, KA, Jang, SY, Sohn, KM, Won, HH, Kim, MJ, Kim, JW & Chung, CS 2007, 'Association between a polymorphism in the lymphotoxin-a promoter region and migraine', Headache, vol. 47, no. 7, pp. 1056-1062. https://doi.org/10.1111/j.1526-4610.2007.00847.x

Association between a polymorphism in the lymphotoxin-a promoter region and migraine. / Lee, Kyung A.; Jang, Soo Yeon; Sohn, Kwang Min; Won, Hong Hee; Kim, Min Ji; Kim, Jong Won; Chung, Chin Sang.

In: Headache, Vol. 47, No. 7, 01.07.2007, p. 1056-1062.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between a polymorphism in the lymphotoxin-a promoter region and migraine

AU - Lee, Kyung A.

AU - Jang, Soo Yeon

AU - Sohn, Kwang Min

AU - Won, Hong Hee

AU - Kim, Min Ji

AU - Kim, Jong Won

AU - Chung, Chin Sang

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Y1 - 2007/7/1

N2 - 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 TNFα in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFα 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 TNFα 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.

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 TNFα in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFα 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 TNFα 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.

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