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.
    DNA and Cell Biology 12/2014; 34(3). DOI:10.1089/dna.2014.2534 · 2.06 Impact Factor
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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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    ABSTRACT: Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people's daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies.
    Current Genomics 08/2013; 14(5):300-315. DOI:10.2174/13892029113149990007 · 2.34 Impact Factor
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    ABSTRACT: Migraine carries a significant hereditary determination. Familial hemiplegic migraine (FHM) has been recently linked to mutations in the CACNA1A gene on chromosome 19. CACNA1A codes for a subunit of a neural calcium channel. Other linkage loci on chromosome 1q21-23 and 1q31 have been reported. Several linkage and association studies have been performed to determine the role of the CACNA1A gene, and of other candidate genes implicated in the metabolism of serotonin and dopamine, in the more common types of migraine. Co-morbidity of migraine with vascular events has been analysed versus genetic prothrombotic factors and mitochondrial DNA, and genes involved in the inflammatory cascade have been explored. Though no definite conclusions have emerged from these studies as yet, molecular genetics of migraine can be expected to unravel the complex aetiologies of these fascinating diseases.
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