PTPN22 and myasthenia gravis: Replication in an Italian population and meta-analysis of literature data

Provenzano, Carlo; Ricciardi, Roberta; Scuderi, Flavia; Maiuri, Maria Teresa; Maestri, Michelangelo; La Carpia, Francesca; Sferrazza, Antonella; Marino, Mariapaola; Leone, Lucia; Lucchi, Marco; Mussi, Alfredo; Zollino, Marcella; Evoli, Amelia; Bartoccioni, Emanuela

doi:10.1016/j.nmd.2011.09.003

« Previous Next »Neuromuscular Disorders
Volume 22, Issue 2 , Pages 131-138, February 2012

PTPN22 and myasthenia gravis: Replication in an Italian population and meta-analysis of literature data

Carlo Provenzano
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
- Corresponding authors. Tel.: +39 06 30154914; fax: +39 06 3386446.
- These authors equally contributed to the present paper.
Roberta Ricciardi
- Department of Neuroscience, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
- Cardiac and Thoracic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
- These authors equally contributed to the present paper.
Flavia Scuderi
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
- These authors equally contributed to the present paper.
Maria Teresa Maiuri
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Michelangelo Maestri
- Department of Neuroscience, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
Francesca La Carpia
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Antonella Sferrazza
- Institute of Hygiene, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Mariapaola Marino
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Lucia Leone
- Institute of Human Physiology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Marco Lucchi
- Cardiac and Thoracic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
Alfredo Mussi
- Cardiac and Thoracic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
Marcella Zollino
- Institute of Medical Genetics, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Amelia Evoli
- Department of Neurological Sciences, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
Emanuela Bartoccioni
- Institute of General Pathology, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy
- Corresponding authors. Tel.: +39 06 30154914; fax: +39 06 3386446.

Received 28 June 2011; accepted 1 September 2011. published online 26 December 2011.

Abstract

Polymorphisms in PTPN22 are associated with many autoimmune diseases; while rs2476601 is supposed to play a major role, other experimental data suggest that rs2488457 may be even more important. Results in myasthenia gravis are controversial. In 356 Italian myasthenic patients and 439 controls genotyped for both polymorphisms, we found that rs2476601 was not associated with myasthenia, presence of autoantibodies, thymus pathology, sex or onset age unlike previous studies on other European populations (confirmed by the present meta-analysis). On the other hand, while rs2488457 was not associated with myasthenia or thymus pathology, we found a correlation of rs2488457 with low autoantibody titers and a trend of association with a less severe disease. Both polymorphisms were in tight linkage disequilibrium in controls, not in patients. Our results suggest that SNPs in this gene different from rs2476601, and/or epigenetic interactions, could play a greater role.

Keywords: Autoimmunity, Ecogenetics, Polymorphism, Acetylcholine receptor, Muscle specific kinase