Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


R577X Alpha-Actinin 3 ACTN3) polymorphism Is Associated with Inflammatory Myopathies in Mexican population.

Sandoval-Garcia1,  Flavio, Petri2,  Marcelo, Saavedra3,  Miguel A., Cruz-Reyes4,  Claudia, Jara-Quezada3,  Luis, Davalos5,  Ingrid, Salazar-Paramo6,  Mario

Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico, Mexico
Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Universidad de Guadalajara, Guadalajara, Jalisco, México, Mexico
Universidad de Guadalajara, Guadalajara, Jalisco, México, Mexico
Hospital Civil JIM
Universidad de Guadalajara, Gudalajara, Jalisco, México, Mexico
Universidad de Guadalajara, Guadalajara, Jalisco, Mexico, Mexico
Centro Medico La Raza Instituto Mexicano del Seguro Social Mexico D.F., México D.F., Mexico
Centro Medico La Raza Instituto Mexicano del Seguro Social Mexico D.F., Mexico D. F., Mexico
Departamento de Biologia Molecular y Genomica, Instituto de Genetica Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico, Mexico
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico, Mexico
Centro Médico Nacional de Occidente, IMSS, Guadalajara, Jalisco, México, Mexico
Hospital Regional de Zona 110, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico, Guadalajara, Jalisco, Mexico, Mexico
Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico, Mexico

Background/Purpose:

Inflammatory myopathies (IM) such as Polymyositis (PM) and Dermatomyositis (DM) are characterized by muscle damage and proximal muscle weakness. The muscle are enriched by alpha-actinins (ACTN) that are cytoskeletal proteins which encode a spectrin superfamily genes tissue–specific for myocardial diseases: ACTN1 and muscle tissues (ACTN2, ACTN3). The function of ACTN heterodimers is to cross-link and bind actin, along with preserving spatial association among myofilaments. ACTN3 expression is restricted to type II fibers (100% of type IIb/x fibers and 50% of type IIa). The ACTN3 gene is located in the region 11q13–14 and in normal conditions, translates a 901 aminoacid protein. The R577X ACTN3 polymorphism is characterized by a non sense polymorphism resulting in the replacing of Arginine (R) by a premature stop codon (X) in the exon 16 (R577X). The homozygous XX are associated with incomplete translation resulting in lost of function of ACTN3. The R577X ACTN3 R allele is related with strength and power muscle phenotype and the X allele is associated with endurance. Since muscle weakness is a common feature in IM, the aim of this study was to analyze the influence of the R577X ACTN3 polymorphism in a group of Mexican patients with PM/DM.

Methods:

37 patients with Dermatomyositis (DM)/ Polymyositis (PM) and 85 healthy subjects were analyzed using PCR-RFLP for the R577X ACTN3 polymorphism. Genotypes and alleles were analyzed. Enzymes such as CPK, LDH, AST and ALT were taken at diagnosis and recruitment to the study.

Results:

We found that 36% XX of healthy subjects were polymorphic for the R577X ACTN3 polymorphism (18% RR and 46% RX) compared with 70% of R577X ACTN3 polymorphic in IM (70% XX, 6% RR and 24% RX). The R allele was present in 41% and X in 59% in healthy subjects compared with 18% of the R and 82% X allele within the IM group (p<0.001). The polymorphic allele X, is associated with the group of IM. Although, within patients with IM, the cases carrying XX genotype had lower levels of enzymes such as CPK, AST and ALT (p<0.01, p<0.01 and p<0.05 respectively) compared with RX genotype.

Conclusion:

In our study since 70% of IM patients were carriers of the R577X ACTN3 polymorphic XX genotype, the lack of the protein could be a genetic factor that facilitates the muscle weakness and poor muscle resistance, besides the inflammatory damage mediated by the immune system itself.

To cite this abstract, please use the following information:
Sandoval-Garcia, Flavio, Petri, Marcelo, Saavedra, Miguel A., Cruz-Reyes, Claudia, Jara-Quezada, Luis, Davalos, Ingrid, et al; R577X Alpha-Actinin 3 ACTN3) polymorphism Is Associated with Inflammatory Myopathies in Mexican population. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :250
DOI:

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