Genetic Variation in Cytokine-Related Genes and Migraine Susceptibility

Abstract

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNF␣, lymphotoxin ␣ (LTA), and lymphotoxin ␤ (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNF␣ contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Tumor Necrosis Factor (TNF) –308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis

“…Among the 11 papers focusing on TNF –308G>A, 7 [ 27 , 28 , 31 , 34 , 36 , 37 , 44 ] reported genotype and allele frequencies for all participants and for overall migraine, as well as stratified by gender and aura; however, the remaining 4 papers did not [ 26 , 30 , 35 , 45 ]. After contacting the authors of these papers, we obtained complete data for one study [ 35 ].…”

“…Among the 11 papers focusing on TNF –308G>A, 7 [ 27 , 28 , 31 , 34 , 36 , 37 , 44 ] reported genotype and allele frequencies for all participants and for overall migraine, as well as stratified by gender and aura; however, the remaining 4 papers did not [ 26 , 30 , 35 , 45 ]. After contacting the authors of these papers, we obtained complete data for one study [ 35 ]. Among the eight papers discussing NOS3 +894G>T, six reported genotype and allele frequencies for all participants and for overall migraine as well as those stratified by aura [ 33 , 38 , 49 – 51 , 53 ], while the remaining two did not [ 27 , 47 ].…”

“…For TNF –308G>A, all studies were of a case-control design [ 26 , 28 – 31 , 34 – 36 , 44 – 46 ] except one that had a cohort design [ 27 ]. One study was performed in children [ 36 ], and the others in adults [ 26 – 32 , 34 , 35 , 45 , 46 ]. Six studies were performed in Caucasians [ 26 , 27 , 32 , 35 , 36 , 46 ] and five in non-Caucasians [ 28 , 30 , 31 , 34 , 45 ].…”

“…One study was performed in children [ 36 ], and the others in adults [ 26 – 32 , 34 , 35 , 45 , 46 ]. Six studies were performed in Caucasians [ 26 , 27 , 32 , 35 , 36 , 46 ] and five in non-Caucasians [ 28 , 30 , 31 , 34 , 45 ]. For NOS3 +894G>T, all studies were of a case-control design, and all studies were performed in adults.…”

Exosomes derived from synovial fibroblasts under hypoxia aggravate rheumatoid arthritis by regulating Treg/Th17 balance

“…RA lesions mainly exist in the synovial joints, such as hands, feet, and knee joints. 5 Joint redness, swelling, heat and pain, and dysfunction are common symptoms in the early stage, and joints with varying degrees of stiffness may appear in the late stage, accompanied by bone destruction and atrophy of skeletal muscle, which can easily cause disability 6 and seriously affect people’s quality of life. Besides, RA complications include pleurisy, pericarditis, and vasculitis, which increase the risk of cancer in severe cases, 7 leading to death and bring heavy economic burden on society and families.…”