Characterising heart rhythm abnormalities associated with Xp22.31 deletion.
Anemia
Arrhythmias, Cardiac
Dermatology
Gastrointestinal Diseases
Genetic Association Studies
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
05
08
2022
accepted:
29
10
2022
medline:
23
6
2023
pubmed:
16
11
2022
entrez:
15
11
2022
Statut:
ppublish
Résumé
Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk. Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers. We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants around Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Sections du résumé
BACKGROUND
Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk.
METHODS
Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers.
RESULTS
We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants around
CONCLUSION
Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Identifiants
pubmed: 36379544
pii: jmg-2022-108862
doi: 10.1136/jmg-2022-108862
pmc: PMC10359567
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
636-643Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222849/Z/21/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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