The TNF-α-308G/A polymorphism is associated with migraine risk: A meta-analysis

Abstract

Abstract. Migraine is a neurasthenia and the genetic etiology has not been determined. Several studies concerning the correlation between the tumor necrosis factor (TNF)-α -308G/A polymorphism and migraine have been published, but their results remain controversial and the small samples in each study do not allow sufficient statistical power. In the present study, odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association between the polymorphism and migraine. An inverse-variance method was applied to estimate the frequency of the putative risk allele in the controls. Heterogeneity was determined using Cochran's Q test and the inconsistency index (I 2 ). Begg's test and the inverted funnel plot were used to assess the publication bias. Five studies on Asian populations, comprising 985 cases and 958 controls, were included in the meta-analysis. The overall results revealed that the TNF-α -308G/A polymorphism was associated with migraine risk in Asians. The ORs were 1.735 (95% CI, 1.129-2.666) for A vs. G; 1.781 (95% CI, 1.166-2.718) for GA vs. GG; 1.821 (95% CI, 1.153-2.874) for AA+GA vs. GG. The subgroup analysis was based on migraine with aura (MA) and migraine without aura (MO) and there was a statistically significant result for MA [the OR was 1.728 (95% CI, 1.095-2.726) for GA vs. GG and 1.651 (95% CI, 1.049-2.598) for AA+GA vs. GG] but not for MO. In conclusion, the TNF-α -308G/A polymorphism was associated with migraine risk. IntroductionMigraine is a common, chronic, recurrent and neurovascular disorder which is associated with digestive system and autonomic nervous system symptoms (1). The two main clinical types are MA (migraine with aura) and MO (migraine without aura). In the general population, 10% of males and 24% of females suffer from migraine (2,3). A review (4) reported that the global incidence of adult migraine is over 10%. It has been confirmed that migraine is associated with other diseases. Research has shown that MA may increase the risk of cardiovascular disease (CVD), myocardial infarction and ischemic stroke in female patients (5). The mortality rate of patients with MA who have CVD and stroke is higher than that of those who do not suffer from migraine (6).However, the pathophysiology of migraine remains unclear. Previously, the vascular hypothesis (7) proposed that migraine was caused by intracranial and extracranial vascular dysfunction. However, this hypothesis did not address neurogenic changes and did not explain the typical migraine (MA) and common migraine (MO) phenomena. Neurogenic inflammation may be a key mechanism in stimulating the trigeminal system and causing the headache.Tumor necrosis factor (TNF) is a pro-inflammatory molecule and a polypeptide effector of the inflammatory reaction which also appears to play a role in migraine. TNF-α activates the transcription of calcitonin gene-related peptide (CGRP) and plays a key role in migraine pathophysiology (8). A study (9) revealed that levels of CGRP in the external jugular vei...

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

“…Therefore, our finding agrees with previous studies which have recognised the role of TNF in the pathogenesis of endometriosis [83,88]. In contrast, contradictory evidence for the role of TNF-α in migraine has been reported [89,90]. Hence, the present study provides important support for TNF-α in both endometriosis and migraine pathogenesis.…”

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

“…Due to the failure of independent association studies in identifying a role for the TNF –308G>A polymorphism in migraine, two meta-analyses were performed to reach definitive and reliable conclusions. Gu et al [ 40 ] performed a meta-analysis associating the TNF –308G>A polymorphism with migraine based on six studies in Asian populations (985 cases and 958 controls); their results indicated that the TNF –308G>A polymorphism was associated with migraine risk in Asians. Subgroup analysis suggested that there was a statistically significant result for MA but not for MO.…”

“…A single study may not have sufficient power to completely demonstrate this complicated genetic relationship because of relatively small sample sizes, and larger studies could overcome these disadvantages. There have been two previous meta-analyses of TNF –308G>A, and the scenario remained virtually unchanged [ 39 , 40 ]. To clarify this association, we performed a meta-analysis of case-control studies to evaluate whether the TNF –308G>A and NOS3 +894G>T polymorphisms confer genetic susceptibility to migraine.…”

Relationship between Vitamin D Receptor Gene Polymorphisms and Migraine without Aura in an Iranian Population

“…Gu et al included five studies on Asian populations in their meta-analysis, including 985 cases and 958 controls. They revealed that the TNF-alpha −308G/A polymorphism was associated with migraine risk [21]. Yilmaz et al in their survey suggested that the IL-1beta gene polymorphism contributes to migraine headache generation in migraine without aura patients [20].…”