rs2651899 variant is associated with risk for migraine without aura from North Indian population

DOI: https://doi.org/10.1007/s11033- 019- 04593- 1

Abstract-Summary For further replicate these findings, we selected two SNPs; rs2651899 on chromo- some 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population.

Univariate and multivariate analyses were done to find the association of differ-

ent genotypes and alleles of these SNPs with migraine and its subgroups.

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2 Mechanisms

We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058–2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169–3.276).

A similar trend was observed both on subgroup and gender analysis in migraine

without aura (MO) and females respectively for rs2651899 variant.

For the other SNP (rs10166942), statistically non-significant differences were reported in the allelic/genotypic frequencies between migraineurs and controls as p > 0.05.

On subgroup analysis we found statistically significant differences at genotypic (p < 0.05) and dominant models in migraine with aura (MA) and in males with that of entire controls.

This research study showed that rs2651899 is a potential genetic marker for migraine susceptibility in MO and female subgroup at both genotypic and allelic level in the North Indian population and found that rs10166942 variant may be a potential marker for MA and male subgroup.

Extended: These findings strengthen the previous association of these variants with migraine pathology and provide new targets for migraine mechanisms and drug therapies.

Introduction Genome-wide association study (GWAS) of migraine revealed three SNPs in or near LRP1, TRPM8 and PRDM16 genes [65].

PRDM16 gene can be used as a candidate marker in future studies by knowing the comorbidity between cardiovascular diseases and migraine, More case control studies with reasonable number of individuals from different geographical regions are needed to explore the relationship of this SNP with migraine [118].

As both migraine and neuropathic pain have certain similar features [119], a study on the role of TRPM8 gene in migraine and a link between both these pain syndromes can be an interesting topic for research scientists.

Study, we investigated two SNPs i.e. rs2651899 and rs10166942 for their asso- ciation between migraine patients and healthy controls from North Indian population.

Materials and Methods We selected 150 unrelated migraine subjects (43 with MA and 107 with MO) from ESIC Medical College & Hospital, Faridabad.

Subjects having neurological disorders, comorbid disorders and non-migrainous

headaches were excluded from this study.

We obtained informed consent in written from all subjects and further this study was approved by Ethics Committees from JMI, New Delhi and from that of ESIC Medical College & Hospital, Faridabad.

This mixture was then incubated overnight at 37 °C with AvaI and at 65 °C with MseI. Digested PCR products were then checked on 3% agarose gel stained with ethidium bromide.

2.1 Genetics

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rs2651899 PCR products of 273 bp were digested into 192 bp and 81 bp for T allele by AvaI enzyme and rs10166942 PCR products of 180 bp were cut into 107 bp and 73 bp fragments for T allele by MseI enzyme at 65 °C.

Results We could not find any statistically difference in terms of age as p = 0.35 on compar- ing migraine patients and healthy controls.

We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 gene polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058–2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169–3.276).

The results of gender analysis for this polymorphism showed a statistically sig- nificant difference at genotypic (p < 0.05), allelic (p = 0.009; OR 0.625; 95% CI 0.440–0.889) and dominant models (p = 0.017; OR 0.498; 95% CI 0.282–0.881) by comparing female migraine patients with entire control.

We did not found any statistically significant difference in female subgroup on

comparing with entire controls at any level for rs10166942 (p > 0.05).

Discussion None of the SNPs specifically associated with migraine subtypes and features in their study which was contradicted with our results as we found statistically signifi- cant differences at genotypic and allelic levels in MO and females.

An and others [120] reported a potential role of rs2658199 variant in Chinese MO migraine susceptibility and found a significant difference in allelic distribution of this SNP between migraine without aura (MO) and control (p = 0.049).

For variant rs10166942, we found no association with migraine on comparing with control at genotypic and allelic levels in this study (p > 0.05) although in sub- group analysis we found a statistically significant difference at genotypic level in MA and male subgroup as p < 0.05.

SNP rs10166942 was replicated in two different studies by Fan and others [121] and An and others [120] and they also reported statistically non-significant differ- ences in allelic or genotypic frequencies between migraine patients and controls and further supported our study.

Conclusion We replicated the association of two variants i.e. rs2658199 and rs10166942 form migraineurs including both migraine with aura and without aura form North Indian population and found that variant rs2658199 is significantly associated with migraine without aura and with female subgroup.

We also reported that rs10166942 variant may be a potential marker for MA and

male subgroup.

Acknowledgement A machine generated summary based on the work of Kaur, Sukhvinder; Ali, Arif; Ahmad, Uzair; Pandey, A. K.; Singh, Balkirat. 2019 in Molecular Biology Reports.

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2 Mechanisms

CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA