BMI and malignant hyperthermia pathogenic ryanodine receptor type 1 sequence variants in Switzerland: A retrospective cohort analysis.
Eur J Anaesthesiol
; 38(7): 751-757, 2021 07 01.
Article
de En
| MEDLINE
| ID: mdl-33259453
ABSTRACT
BACKGROUND:
Ryanodine receptor type 1 (RYR1) sequence variants are pathogenic for malignant hyperthermia. Variant carriers have a subtle increase in resting myoplasmic calcium concentration compared with nonaffected individuals, but whether this has metabolic effects in daily life is unknown.OBJECTIVES:
We analysed the potential effect of malignant hyperthermia-pathogenic RYR1 sequence variants on BMI as a single factor. Due to the heterogeneity of genetic variants predisposing to malignant hyperthermia, and to incomplete information about their regional distribution, we describe the prevalence of RYR1 variants in our population.DESIGN:
A retrospective cohort study.SETTING:
A single University hospital. PATIENTS Patients from malignant hyperthermia families with pathogenic RYR1 sequence variants were selected if BMI was available. OUTCOMEMEASURES:
BMI values were compared amongst malignant hyperthermia susceptible (MHS) and malignant hyperthermia-negative individuals using hierarchical multivariable analyses adjusted for age and sex and considering family clustering. Variant prevalence was calculated.RESULTS:
The study included 281 individuals from 42 unrelated malignant hyperthermia families, 109 of whom were MHS and carriers of the familial RYR1 sequence variants. Median [IQR] BMI in MHS individuals with pathogenic RYR1 variants was 22.5âkgâm-2 [21.3 to 25.6âkgâm-2]. In malignant hyperthermia-negative individuals without variants, median BMI was 23.4âkgâm-2 [21.0 to 26.3âkgâm-2]. Using multivariable regression adjusted for age and sex, the mean difference was -0.73 (95% CI -1.51 to 0.05). No carrier of a pathogenic RYR1 sequence variant was found to have BMI higher than 30âkgâm-2. Only 10 RYR1 variants from the list of the European MH Group were found in our cohort, the most common being p.Val2168Met (39% of families), p.Arg2336His (24%) and p.Arg614Cys (12%).CONCLUSION:
The observed tendency towards lower BMI values in carriers of malignant hyperthermia-pathogenic RYR1 sequence variants points to a possible protective effect on obesity. This study confirms regional differences of the prevalence of malignant hyperthermia-pathogenic RYR1 sequence variants, with just three variants covering 75% of Swiss MHS families. TRIAL REGISTRATION This manuscript is based on a retrospective analysis.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Canal de libération du calcium du récepteur à la ryanodine
/
Hyperthermie maligne
Type d'étude:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limites:
Humans
Pays/Région comme sujet:
Europa
Langue:
En
Journal:
Eur J Anaesthesiol
Sujet du journal:
ANESTESIOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
Suisse