MLC1 Polymorphisms Are Specifically Associated with Periodic Catatonia, a Subgroup of Chronic Schizophrenia
Received 17 June 2006; received in revised form 10 August 2006; accepted 15 August 2006. published online 09 January 2007.
Background
The MLC1, located on chromosome 22q13.33, has been suggested as a risk gene for schizophrenia, especially the periodic catatonia subtype. An initially identified missense mutation was found to be extremely rare in other patient cohorts; however, a recent report again argued for an association of two intronic MLC1 single nucleotide polymorphisms (SNPs) with schizophrenia and bipolar disorder.
Methods
A case-control study of these polymorphisms as well as SNPs in the transcriptional control region of MLC1 was conducted in 212 chronic schizophrenic patients, 56 of which suffered from periodic catatonia, 106 bipolar patients, and 284 controls.
Results
Both intronic and promoter polymorphisms were specifically and significantly associated with periodic catatonia but not schizophrenia or bipolar disorder in general. A haplotype constructed from all polymorphisms was also associated with periodic catatonia.
Conclusions
The MLC1 variation is associated with periodic catatonia; whether it constitutes a susceptibility or a modifier gene has to be determined.
aDepartment of Psychiatry and Psychotherapy (Molecular and Clinical Psychobiology), University of Würzburg, Würzburg
bDifferential and Personality Psychology, Institute of Psychology II, Technische Universität Dresden, Dresden
cDepartment of Neuro-Behavioral Genetics, University of Trier, Trier, Germany.
Address reprint requests to Andreas Reif, M.D., Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, D-97080 Würzburg, Germany
ABSTRACT