Inheritance of a common androgen synthesis variant allele is associated with female COVID susceptibility in UK Biobank

McManus, Jeffrey M.; Sabharwal, Navin; Bazeley, Peter; Sharifi, Nima

doi:10.1101/2020.08.27.20183004

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…There are several enzymes that convert adrenal androgens to testosterone and/or DHT have increased expression in castration-resistant disease (12). One such enzyme is 3b-hydroxysteroid dehydrogenase isoenzyme-1 (3b-HSD1, encoded by HSD3B1), which catalyzes the rate-limiting step of potent androgen synthesis from adrenal precursor steroids in peripheral tissues (e.g., prostate, breast, skin, placenta) (13,14). Here, the study discusses the impact of an A→C missenseencoding single nucleotide polymorphism (SNP) in HSD3B1 nucleotide position 1245 (clustered refSNP ID 1047303) to augment potent androgen synthesis from adrenal precursors.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism of 3β-Hydroxysteroid Dehydrogenase-1 in patients with prostate cancer in middle Euphrates of Iraq

Abdyaser

Alta'ee

Joodi

2022

ijhs

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Androgens play critical roles in prostate carcinogenesis as well as prostate cancer progression. Androgen-deprivation therapy (ADT), which reduces testosterone production and inhibits androgen action in prostate cancer cells, has been the criterion standard therapy for metastatic prostate cancer (1). Although initially most prostate cancers respond well to ADT, most patients eventually progress to castration-resistant prostate cancer (CRPC), which is mainly thought to be because androgen receptor reactivation is induced by several mechanisms. One of those mechanisms have been identified to be intratumoral androgen synthesis mostly from adrenal precursor steroids and at least in part due to de novo synthesis from cholesterol which is supported by increased expression of several genes encoding steroidogenic enzymes including HSD3B, HSD17B, and SRD5A in CRPC. Among them, HSD3B1 gene encodes 3β-hydroxysteroid dehydrogenase-1, which is mainly expressed in peripheral tissues including the prostate (another isoform, 3β-hydroxysteroid dehydrogenase-2 was mainly expressed in adrenal gland and gonad in human) and is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis. Genetic polymorphism in HSD3B1 encoding 3β-hydroxysteroid dehydrogenase-1 has been shown to be associated with oncological outcome for prostate cancer. This study to investigate the significance of missense polymorphism in HSD3B1 gene (rs1047303) among men with prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Polymorphism of 3β-Hydroxysteroid Dehydrogenase-1 in patients with prostate cancer in middle Euphrates of Iraq

Abdyaser

Alta'ee

Joodi

2022

ijhs

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“…[ 52 ] This could be due to the prevalence of adrenal permissive HSD3B1 allele among the Spanish population. [ 53 ]…”

Section: Discussionmentioning

confidence: 99%

Gender and genetic factors impacting COVID-19 severity

Mishra

Ranjan

Ravindra

2021

J Family Med Prim Care

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COVID-19 pandemic is a cause of global concern and is impacting lives and economy globally. Infection due to SARS-CoV-2 leads to varied clinical manifestations, which can vary from asymptomatic to severe acute respiratory syndrome and death. The clinical features are proposed to depend upon various host factors, namely, gender and genetic factors. The significantly high mortality among males has revealed the role of gender, androgens, age, genetics, and risk factors in determining the severity of COVID-19 among the population. The interplay of various host factors and their association with clinically severe infections is crucial for our understanding of COVID-19 pathogenesis. A PubMed and Google scholar search was made using keywords such as “COVID-19 + sex differences,” “COVID-19 + androgens,” “COVID-19 + ACE2 receptor,” and “COVID-19 + smoking alcoholism pregnancy.” The articles which highlight the association of gender and genetic factors to COVID-19 were selected and included in our study. It is mainly the primary care or family physicians who act as the first contact of COVID-19 patients. With the recent increase in SARS-CoV-2 infections in the Indian subcontinent and probability of upcoming surges, it has become imperative to understand its interaction with the various gender and genetic factors to devise effective triage and management protocols. Our review highlights the possible mechanisms by which these factors impact the severity of COVID-19. A better understanding of these factors will be of immense help to primary care physicians.

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Inheritance of a common androgen synthesis variant allele is associated with female COVID susceptibility in UK Biobank

McManus

Sabharwal

Bazeley

et al. 2020

Preprint

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A sex discordance in COVID exists, with males disproportionately affected. More broadly, sex differences in infectious and inflammatory processes are well known, with women tending to mount stronger immune responses than men. Although there is evidence that sex hormone signaling is immunomodulatory, including downregulation of immune/inflammatory responses by androgens, the existence of numerous other physiologic differences between the sexes leads to great uncertainty in attributing worse infectious disease outcomes in men to androgen signaling. No definitive genetic data exist to support androgen-mediated immune suppression for viral susceptibility, nor for adrenal androgens. Here we show an association between inheritance of the common adrenal-permissive missense-encoding variant HSD3B1(1245C), that enables androgen synthesis from adrenal precursors10, and susceptibility to COVID. The adrenal-permissive HSD3B1(1245C) has previously been linked to suppression of inflammation in severe asthma. In analysis of COVID test results from the UK Biobank, we show that in older (≥ 70 years of age) subjects, the adrenal-permissive variant is associated with a greater chance of being COVID-positive. The effect increases with the number of HSD3B1(1245C) alleles inherited and is greater in females such that increasing androgen synthesis confers risk approaching males. Our study suggests that a common androgen synthesis variant regulates immune susceptibility to COVID infection as well as potentially other immune and inflammatory processes.

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Inheritance of a common androgen synthesis variant allele is associated with female COVID susceptibility in UK Biobank

Cited by 3 publications

References 57 publications

Polymorphism of 3β-Hydroxysteroid Dehydrogenase-1 in patients with prostate cancer in middle Euphrates of Iraq

Polymorphism of 3β-Hydroxysteroid Dehydrogenase-1 in patients with prostate cancer in middle Euphrates of Iraq

Gender and genetic factors impacting COVID-19 severity

Inheritance of a common androgen synthesis variant allele is associated with female COVID susceptibility in UK Biobank

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