Abstract
BackgroundThe present study was undertaken to find out the role of estrogen pathway related gene polymorphisms in susceptibility to migraine in Northern Indian population. Aromatase, CYP19A1 (rs10046 and rs4646); estrogen receptors, ESR1 (rs2234693, rs1801132, rs2228480 and rs9340799) and ESR2 (rs1271572 and rs1256049) polymorphisms were selected for the present study.Methodology/Principal FindingsThe patients were recruited in two cohorts – primary (207) and replicative (127) along with 200 healthy controls and genotyped for various polymorphisms. Logistic regression analysis was applied for statistical analyses. The results were validated in the replicative cohort and pooled by meta analysis using Fisher's and Mantel-Haenszel test. Furthermore, Benjamini – Hochberg false discovery rate test was used to correct for multiple comparisons. CYP19A1 rs10046 and CYP19A1 rs4646 polymorphisms were found to confer risk and protective effect, respectively. Out of four ESR1 polymorphisms, only rs2234693 variant allele was significantly associated in migraine with aura. No significant associations were observed for ESR2 polymorphisms. Significant haplotypes were identified for CYP19A1 and ESR1 polymorphisms. Gene- gene interactions of genotypes as well as haplotypes were observed for CYP19A1- ESR1 showing both risk and protective combinations.ConclusionWe strongly suggest CYP19A1 polymorphisms to be the major contributing factors in migraine susceptibility instead of genetic variants of estrogen receptors.
Highlights
Migraine is a debilitating neurological disorder affecting about 10% of world’s population [1]
The CYP19A1, ESR1 and ESR2 polymorphisms were selected for the present study
Significant associations were observed for TT genotype in both migraines without and with aura (MA)
Summary
Migraine is a debilitating neurological disorder affecting about 10% of world’s population [1]. It can be broadly classified into two types- Migraine without aura (MO) and Migraine with aura (MA). It is a complex disorder involving interplay between genes and environmental factors. Fluctuating hormone (especially estrogen) levels in women are considered to be the major contributing factors. A detailed understanding of the polymorphisms and their functional effects may provide useful insights in the field of migraine pathophysiology. The present study was undertaken to find out the role of estrogen pathway related gene polymorphisms in susceptibility to migraine in Northern Indian population. CYP19A1 (rs10046 and rs4646); estrogen receptors, ESR1 (rs2234693, rs1801132, rs2228480 and rs9340799) and ESR2 (rs1271572 and rs1256049) polymorphisms were selected for the present study
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