title: Genotype modulators of clinical severity in McArdle disease.
abstract: The phenotypic manifestation of McArdle disease varies considerably from one individual to the next. The purpose of this study was to assess the possible association between the clinical severity of the disease, and each of the genotypes PYGM (R50X), ACE (I/D), AMPD1 (Q12X), PPARGC1A (G482S) and ACTN3 (R577X). We also assessed links between clinical disease severity and other potential phenotype modulators such as age or gender. McArdle disease was diagnosed in 99 patients of Spanish origin (60 male, 39 female; age range 8-81 years) by identifying the two mutant alleles of the PYGM gene. Disease severity was assessed using the grading scheme previously reported by Martinuzzi et al. [A. Martinuzzi, E. Sartori, M. Fanin, et al., Phenotype modulators in myophosphorylase deficiency, Ann. Neurol. 53 (2003) 497-502]. Significant correlation was observed (exact two-sided P<0.0001) between the number of D alleles of the ACE gene and the disease severity score. Rank-order correlation coefficients were 0.296 (95% CI: 0.169, 0.423) (Kendall's tau) and 0.345 (95% CI: 0.204, 0.486) (Somer's D). No significant relationships were detected between clinical severity and the remaining genotypes examined. Finally, disease severity was significantly worse in women with the disease. Our findings indicate that both ACE genotype and gender contribute to how McArdle disease manifests in an individual patient. The role of other candidate genes remains to be elucidated.
authors.affiliation: Centro de Investigación, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Rubio
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.forename: Inés
authors.initials: I
authors.lastname: García-Consuegra
authors.forename: Margarita
authors.initials: M
authors.lastname: Pérez
authors.forename: María I
authors.initials: MI
authors.lastname: Barriopedro
authors.forename: Antoni L
authors.initials: AL
authors.lastname: Andreu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D005260:Female; D005838:Genotype; D006012:Glycogen Storage Disease Type V / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012737:Sex Factors
chemical_list: D007703:Peptidyl-Dipeptidase A