Association of MTHFR gene polymorphisms with migraine in North Indian population

DOI: https://doi.org/10.1007/s10072- 018- 3276- 7

Abstract-Summary The aim of present case-control study was to determine the association between MTHFR gene polymorphisms (C667T; rs 1801133, A1298C; rs 1801131) with migraine susceptibility.

2.1 Genetics

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Genotypic results indicated a non-significant increase in frequencies of CT and TT in C667T SNP in migraine patients with control (52 and 10% vs. 42 and 7%: p > 0.05), but CC genotype in A1298C was found to be a risk factor in migraine patients than controls (30 vs. 17% respectively: p < 0.05).

On comparing migraine subclasses, migraine with aura (MA) and without aura (MO) with control groups, the present study suggests that in MTHFR polymor- phisms, the prevalence of 677CT genotype and T allele in C667T SNP influences susceptibility to MA (p < 0.05) but not to MO.

CC genotype in A1298C SNP could be a risk factor for migraine patients without

aura (p < 0.05).

Introduction The headache associated with migraines may be caused by blood vessels dilating abnormally, and the “aura”—blind spots, flashes of light, and abnormal sensations experienced before the headache—may be caused by slow electrical waves spread- ing out across the brain from where the migraine originates.

Migraines are extremely painful headaches and are caused by a neurological

disorder in the brain.

Many genes have been considered as predisposing factors in initiating migraine

attacks mainly in MA than in MO [3].

Many studies have indicated various susceptibility genes for common migraine

including MTHFR and some other genes [143, 144].

The endothelial damage induced by high levels of homocysteine could decrease nitric oxide release and leads to the initiation and maintenance of migraine attacks [145].

We undertook the case control study to see whether an association exists between MTHFR gene polymorphisms (C667T; rs 1801133 and A1298C; rs 1801131) and migraine patients in North Indian population.

Materials and Methods One hundred migraine patients were selected from those who came to OPD in ESIC Medical College & Hospital, Faridabad.

Further restriction digestion of PCR products was done by HinfI and MboII restriction enzymes (Fermentas, USA) to identify specific alleles in C677T and A1298C polymorphisms, respectively.

The digestion reaction for each PCR product was carried out in a final volume of 20 μL containing 2 μL buffer, 0.1 μL restriction enzyme and 10 μL PCR product.

Digested products were visualized on 3% agarose gel stained with ethidium

bromide.

C677T PCR product (198 bp) was digested into 175 and 23 bp fragments by Hinf

I for T allele.

A1298C PCR product (256 bp) was digested into 212, 183, 30, 28, and 14 bp

fragments by Mbo II for C allele.

The risk of migraine for mutant allele carriers was reported as odds ratios (OR)

and 95% confidence intervals between groups.

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2 Mechanisms

Results A significantly higher frequency of CC in A1298C was observed in patients as com- pared to controls (30 and 17% respectively, p < 0.05) that was associated with increased risk of migraine in patients (OR = 2.15; 95%CI: 1.04–4.44).

Even non-significant higher frequency of T allele was observed in MO against controls (33.7 vs. 28%) which reveal that T allele could be a risk factor for migraine patients in both subgroups.

In MA subgroup of migraine in A1298C polymorphism, a non-significant increase in CC genotype had been found against control (26.1% vs. 17% respec- tively, p > 0.05).

In A1298C SNP the frequency of CC genotype was non-significantly higher in MO (31.2%) vs. MA (26.1%), but the C allele was almost equal in MO (50.7%) and MA (50%) groups of migraine.

Discussion As candidate genes using case control study is a powerful method, we compared the association of C667T (rs 1801133) and A1298C (1801131) polymorphisms in MTHFR gene in migraine patients with healthy controls.

Results showed that CT and TT genotype in C667T were more prevalent in migraine as compared with control group, whereas 1298CC genotype was more common in migraine patients and these results were in compliance with findings shown by Loenz A.L. and others [146] and Bahadir A and others [147] that showed higher frequencies of minor alleles of A1298C and C667T in migraine patients.

A meta-analysis combining all studies assessing the association of MTHFR C677T polymorphism with migraine further suggests that the TT-genotype is a genetic risk factor for migraine with aura, but not to migraine overall [148].

Another study by Saeedi and others [149] indicated that the prevalence of the MTHFR genotypes 677TT/AC1298 were significantly associated with migraine than control (p < 0.01).

Conclusion We conclude that MTHFR polymorphisms are not significantly associated with a risk for the development of migraine in our study.

That polymorphisms in this gene alone cannot serve as a predictive factor for the

risk of migraine.

To understand pathophysiology of migraine condition properly, more studies

including genetic, clinical, and biochemical parameters should be done.

Acknowledgement A machine generated summary based on the work of Kaur, Sukhvinder; Ali, Arif; Pandey, Anil Kumar; Singh, Balkirat. 2018 in Neurological Sciences.

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