Progesterone Receptor Gene (PROGINS) Polymorphism Correlates with Late Onset of Migraine

Palmirotta, Raffaele; Barbanti, Piero; Ialongo, Cristiano; Marchis, Maria Laura De; Alessandroni, Jhessica; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Valente, Maria Giovanna; Ferroni, Patrizia; Della-Morte, David

doi:10.1089/dna.2014.2534

Cited by 12 publications

(6 citation statements)

References 30 publications

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“…A study investigating the relationship between the progesterone receptor gene and migraine found that an PGR polymorphism was not directly connected to predisposition to migraine, however, it led to a later onset of migraine supposedly through reduced neuronal excitability in the brain (109). However, this finding was only observed in females due to the small number of male participants in the study (109).…”

Section: Genetics and Biomarkersmentioning

confidence: 92%

Giving Researchers a Headache – Sex and Gender Differences in Migraine

et al. 2020

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Migraine is a common neurovascular disorder affecting ∼15% of the general population. Ranking second in the list of years lived with disability (YLD), people living with migraine are greatly impacted by this especially burdensome primary headache disorder. In ∼30% of individuals with migraine, transient neurological symptoms occur (migraine aura) that further increase migraine burden. However, migraine burden is differential with respect to sex. Though one-year prevalences in childhood are similar, starting with puberty, migraine incidence increases at a much higher rate in females than males. Thus, migraine over the life course occurs in women three to four times more often than in men. Attacks are also more severe in women, leading to greater disability and a longer recovery period. The sex disparity in migraine is believed to be partly mediated through fluctuations in ovarian steroid hormones, especially estrogen and progesterone, although the exact mechanisms are not yet completely understood. The release of the neuropeptide calcitonin gene-related peptide (CGRP), followed by activation of the trigeminovascular system, is thought to play a key role in the migraine pathophysiology. Given the burden of migraine and its disproportionate distribution, the underlying cause(s) for the observed differences between sexes in the incidence, frequency, and intensity of migraine attacks must be better understood. Relevant biological as well as behavioral differences must be taken into account. To evaluate the scope of the existing knowledge on the issue of biological sex as well as gender differences in migraine, we conducted a systematized review of the currently available research. The review seeks to harmonize existing knowledge on the topic across the domains of biological/preclinical, clinical, and population-level research, which are traditionally synthesized and interpreted in isolation. Ultimately, we identify knowledge gaps and set priorities for further interdisciplinary and informed research on sex and gender differences as well as gender-specific therapies in migraine.

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Section: Genetics and Biomarkersmentioning

confidence: 92%

Giving Researchers a Headache – Sex and Gender Differences in Migraine

et al. 2020

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“…2018 ), ovarian and endometrial cancer ( Liu et al. 2014 ), migraine ( Palmirotta et al. 2015 ), and endometriosis ( Wieser et al.…”

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confidence: 99%

The Neandertal Progesterone Receptor

Zeberg

Kelso

Pääbo

2020

Molecular Biology and Evolution

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The hormone progesterone is important for preparing the uterine lining for egg implantation and for maintaining the early stages of pregnancy. The gene encoding the progesterone receptor (PGR) carries introgressed Neandertal haplotypes with two missense substitutions and a mobile Alu element. These Neandertal gene variants have reached nearly 20% frequency in non-Africans and have been associated with preterm birth. Here, we show that one of the missense substitutions appears fixed in Neandertals, while the other substitution as well as the Alu insertion were polymorphic among Neandertals. We show that two Neandertal haplotypes carrying the PGR gene entered the modern human population and that present-day carriers of the Neandertal haplotypes express higher levels of the receptor. In a cohort of present-day Britons, these carriers have more siblings, fewer miscarriages, and less bleeding during early pregnancy suggesting that the Neandertal progesterone receptor alleles promote fertility. This may explain their high frequency in modern human populations.

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“…Given the strong influence of female gender and sex female hormones on migraine susceptibility, we also investigated the possible association of the rs1042838 polymorphism of Progesterone receptor gene (PGR) with this disease. Indeed, our data highlighted a linear relationship between the copy number of the T allele and the age of migraine onset[ 5 ]. Finally, we excluded any correlation between polymorphisms rs4818 and rs4680 of Catechol-O-Methyltransferase (COMT) gene and migraine, suggesting to look over COMT to explain catecholamine derangement in migraine, exploring enzymes involved in catecholamines synthesis and catabolism such as monoamine-oxidase, dopamine beta hydroxylase, tyrosine hydroxylase or tyrosine decarboxylase[ 6 ].…”

Section: Resultsmentioning

confidence: 99%