Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine

Abstract

Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case–control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5′-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523–0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117–2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140–2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.

NGF gene polymorphisms are not associated with heroin dependence in a Taiwanese male population

“…In addition, variants differing in allele frequencies between populations should also be considered. For example, the A allele frequencies of rs6330 between different ethnic groups were about 30–40% in Caucasian populations, and 12.8% in our Han Chinese population. Although recruiting pure Han Chinese Taiwanese participants may have minimized the effects of population stratification, further studies for other ethnic groups were warranted, to confirm our study results.…”

Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine Susceptibility: A Meta-analysis of Case–Control Studies

“…The results showed that statistical significance of the allelic (Figure 3A) or the dominant (Figure 3B) model of rs6265 was lost when the study of Coskun et al (21) was excluded from the analysis (dominant OR: 1.17, 95% CI: 1.00–1.38, p  = 0.054; allelic OR: 1.14, 95% CI: 0.99–1.31, p  = 0.067). To assess the potential effects of specific study characteristics on the association between rs6265 and migraine susceptibility, we pooled the OR and 95% CI from the subgroups of migraine type and study quality.…”

“…Methodological items for quality assessment and individual item scores of each included study are illustrated in Table 2. Three studies were classified as “higher” quality studies (19–21), while the remaining two studies were rated as “lower” quality studies (18, 25). Genotypic data for the BDNF gene rs6265 were available in four studies as subgroups of migraine with and without aura (18, 20, 21, 25).…”

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

“…Recent studies reported that rs6330, rs2072446 and rs734194 genetic variants are associated with number of neurovascular and psychiatric diseases, which might predispose to stroke and increase its likelihood [ 23 , 24 ]. Particularly, it was shown that NGF rs6330*T minor allele is positively associated with the risk of migraine, schizophrenia and Alzheimer’s disease [ 13 , 14 , 25 ]. As for NGFR rs2072446, it was observed as being associated with depression and schizophrenia [ 13 , 15 ].…”