Association of estrogen receptor α polymorphism rs1999805 with asthma

Abstract

phenome-wide association study (PheWAS); asthma; estrogen receptor α As adults, women have higher rates of asthma and allergic disease as well as increased asthma severity compared to men. 1 Pre or peri-menstrual worsening of asthma symptoms (PMA) were reported in 17% of women enrolled in the severe asthma research program, with 52% of these women with PMA having severe asthma. 2, 3 Further, use of birth control medications or hormone replacement therapy during peri or post-menopause was also linked to worsening of asthma in some women. 2,4 Mouse models of asthma showed estrogen signaling through estrogen receptor-alpha (ER-α), and not ER-β, increased allergic airway inflammation, mucus production, and/or airway hyperresponsiveness. 2,4 Collectively, these findings suggest a critical role for ER-α signaling in asthma pathogenesis.

Associations between prenatal exposure to DDT and DDE and allergy symptoms and diagnoses in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), South Africa

“…This may occur through endocrine disruption as p,p'-DDT and o,p'-DDT are estrogenic while p,p'-DDE is anti-androgenic (143)(144)(145)(146)(147)(148). Moreover, epidemiological studies strongly suggest that sex hormones play an important role in the etiology of allergies, particularly for asthma and allergic rhinitis (149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163)(164). While a higher incidence of asthma, wheeze and rhinitis is observed in young boys, a gender switch occurs around puberty when the incidence becomes substantially higher among females (149,154,158,163,(165)(166)(167).…”

Sex Differences in Otolaryngology: Focus on the Emerging Role of Estrogens in Inflammatory and Pro-Resolving Responses

“…The persistent inflammation of the sinus epithelium, often linked to the accumulation of immune cells (i.e., eosinophils) with inflammatory signals, is intensified into a route in which the natural healing process is misoriented, eventually leading to the destruction of the nasal epithelium [53,198]. Although the underlying role of estrogens in regulating the resolution of uncontrolled inflammation in CRSwNP remains largely unknown, ER polymorphism has been implicated in female airway hypersensitivity and asthma through regulation of the activities of eosinophils, and the regulatory machinery might also play a role in resolving CRSwNP [58,59]. To resolve uncontrolled inflammatory responses, a natural preresolving mechanism that is critical in maintaining tissue homeostasis is apparently altered in CRSwNP under the influence of estrogens [60,61].…”

Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment

“…Additionally, an expression analysis has reported the expression of ER and PR in mast cells of human upper airways where they have been known to activate mast cells ( 118 , 119 ). Differential expression of ER in asthmatics and receptor polymorphism have also been held accountable for elevating the asthma pathogenesis ( 120 , 121 ). Interestingly, the role of ERβ differs from that of ERα and few recent studies have demonstrated its protective role in asthma via inhibition of PDGF induced proliferation, suppression of the NF-κB pathway, downregulation of AHR and airway remodeling ( 122 – 126 ).…”