There are significant differences in allelic distributions for rs2234693 and rs9340799 in ESR1 gene between patients with migraine and control subjects.
Both 325C>G and 594G>A polymorphisms showed no major effects either in males or in females.Based on the statistical data, we conclude some of the ESR1 gene polymorphisms may have major contributions to the pathogenesis of migraine in Caucasian populations.
Effect estimates from an additive model suggest that the ESR-1 594 G>A (pooled OR 1.37; 95% CI 1.02-1.83) and ESR-1 325 C>G (pooled OR 1.16; 95% CI 1.03-1.32) variants are associated with any migraine.
We found significant association of TT genotype [odds ratio (OR) 3.458, confidence interval (CI) 1.757, 6.806; P = 0.0003] and T allele (OR 1.729, CI 1.309, 2.284; P = 0.0001) of ESR1 PvuII single nucleotide polymorphism with migraine when compared with HC.
Using the SUMSTAT program, we observed ESR2-ESR1-FSHR significant gene-gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females).We corroborated that ESR2-ESR1-FSHR haplotypes interacted for migraine under a model-free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e-4, under the heterogeneity model; P = .001 for females).
In this study, we tested the association of two female hormonal genes, progesterone receptor (PGR) and estrogen receptor (ESR1), which were previously reported to be associated with migraine in women.
There were no differences in the genotype distributions of the previously migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and controls (P-values 0.83 and 0.55, respectively).
Interaction analysis of the PROGINS variant with our previously reported associated ESR1 594A variant showed that individuals who possessed at least one copy of both risk alleles were 3.2 times more likely to suffer migraine.
A population-based cohort of 224 migraine sufferers and 224 matched controls were genotyped for the G594A polymorphism located in exon 8 of the ESR1 gene.
A population-based cohort of 224 migraine sufferers and 224 matched controls were genotyped for the G594A polymorphism located in exon 8 of the ESR1 gene.