Association of progesterone receptor with migraine-associated vertigo

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Neurogenetics (Impact Factor: 2.88). 09/2007; 8(3):195-200. DOI: 10.1007/s10048-007-0091-3
Source: PubMed


While migraine has been demonstrated to be familial and have genetic contributions, genome-wide linkage analyses and candidate gene studies have highlighted that migraine is genetically complex. Despite substantial efforts, no consistent replication of linkage or association has been reported for common migraine syndromes. Among the candidate genes tested for association with migraine by several groups were female sex hormone genes based on the observation of a much higher incidence of migraine in females. Migraine-associated vertigo (MAV) is a migraine syndrome also much more common in females than males. Because MAV is less common in the general population than migraine or migraine with aura, it may be a better migraine syndrome to detect susceptibility alleles. 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. We typed 150 MAV subjects and 145 genomic matched control subjects. One SNP (rs1042838) within PGR, which is in high linkage disequilibrium with the functional PROGINS variant, was significantly associated with MAV (p = 0.0007). Two SNPs (rs2228480 and rs1801132) within ESR1 demonstrated no significant association. No synergistic effect between ESR1 variants and PGR variants was identified.

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Available from: Stanley F Nelson, Jul 07, 2015
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    • "However, a new clinically useful finding from this study is the evidence of an association between rs1042838 TT genotype, indicative of the ''PROGINS variant haplotype,'' and a delayed age of migraine onset compared with GT and GG genotypes, with a linear relationship in the MwA female patient group. Interestingly, in a precedent study performed on 150 migraine patients selected for the presence of concomitant vertigo (migraine-associated vertigo [MAV]), Lee et al. (2007) reported that the PGR PROGINS variant allele T of rs1042838 was significantly associated with MAV. We could not test this effect in our study, as only a few patients had vertigo, a symptom that is more frequent in young migraineurs. "
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    ABSTRACT: Progesterone influences central neuronal excitability, a key event in migraine pathophysiology. Progesterone receptor gene (PGR) rs1042838 (G/T - Val660Leu) variant is indicative of PROGINS haplotype and associated to a reduced PGR activity. With the aim of investigating whether any type of association existed between this genetic variant and migraine pathophysiology, genotyping was performed in 380 consecutive migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls from Interinstitutional Multidisciplinary BioBank (BioBIM) of IRCCS San Raffaele Pisana, Rome, Italy. rs1042838 genotypes did not correlate with demographics or clinical migraine features. However, TT (Leu) genotype was significantly associated with a later age of migraine onset: Patients affected by migraine with aura showed a linear relationship between copy number of the T allele carried by the individual and the age of migraine onset. Our data suggest that the PROGINS PGR polymorphism does not directly predispose to migraine but significantly delays migraine onset probably via a reduction in brain neuronal excitability.
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    • "Subsequent to the estrogen receptor, the PROGINS variant (a 306 base pair insertion within intron 7) in PGR located on chromosome 11q22, was next investigated by Colson et al., 2005 in the same Caucasian population. Colson et al., 2005 found a positive association again only to be replicated by Lee et al., 2007 in patients with migraine-associated vertigo and Joshi et al., 2010 in a north Indian population [147]. Interestingly when the original authors analyzed the interaction of both hormonal genes together (ESR1 594A allele and PROGINS variant) they identified a synergistic effect whereby migraine risk was increased 3.2 times [148]. "
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