Korean J Schizophr Res.  2014 Apr;17(1):43-46. 10.16946/kjsr.2014.17.1.43.

The PTPRD (Protein Tyrosine Phosphatase Receptor Type Delta) Gene Polymorphism and Antipsychotic-Induced Restless Legs Syndrome in Schizophrenia

• Jung HJ
• Cho CH
• Kang SG
• Lee HJ

• KMID: 2288298
• DOI: http://doi.org/10.16946/kjsr.2014.17.1.43

Abstract

OBJECTIVES
The previous genome-wide association studies have revealed several candidate genes for restless legs syndrome (RLS). The PTPRD (protein tyrosine phosphatase receptor type delta) gene is one of the candidate genes for RLS. The occurrence of antipsychotic-related RLS could also be attributable to differences in genetic susceptibility. This study aimed to investigate whether PTPRD polymorphism is associated with antipsychotic-related RLS in schizophrenia.
METHODS
We assessed symptoms of antipsychotic-induced RLS in 190 Korean schizophrenic patients and divided the subjects into two groups according to the International Restless Legs Syndrome Study Group diagnostic criteria : (i) subjects that met all of the criteria (n=44) and (ii) the remaining subjects who were not considered to be RLS patients (n=146). PTPRD rs462664 was genotyped by PCR in 190 individuals. The chi2-test was performed to compare differences between two groups.
RESULTS
The frequencies of genotype (chi2=1.31, p=0.519) of the PTPRD rs462664 did not differ significantly between schizophrenic patients with and without RLS. The difference of allele frequencies (chi2=1.30, p=0.25) of the PTPRD rs462664 between the schizophrenic patients with and without RLS were not significant.
CONCLUSION
These results suggest that PTPRD gene polymorphism does not play a major role in susceptibility to antipsychotic-related RLS in schizophrenia. This finding suggests that antipsychotic-induced RLS may have a different pathogenesis compared to primary RLS.

Keyword

Restless legs syndrome; PTPRD; Schizophrenia

MeSH Terms

Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Polymerase Chain Reaction
Restless Legs Syndrome*
Schizophrenia*
Tyrosine*
Tyrosine

Reference

References

1. Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep. 1994; 17:739–743.

2. Desautels A, Turecki G, Montplaisi J, Xiong L, Walters AS, Ehrenberg BL, et al. Restless legs syndrome: confirmation of linkage to Chromosome 12q, genetic heterogeneity, and evidence of complexity. Arch Neurol. 2005; 62:591–596.

3. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilza-deh S, et al. Genomewide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet. 2007; 39:1000–1006.

4. Stefansson H, Rye DB, Hicks A, Petursson H, Ingason A, Thorgeirs-son TE, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2007; 357:639–647.

5. Kang SG, Lee HJ, Kim L. Restless legs syndrome and periodic limb movements during sleep probably associated with olanzapine. J Psychopharmacol. 2009; 23:597–601.

6. Kang SG, Lee HJ, Jung SW, Cho SN, Han C, Kim YK, et al. Characteristics and clinical correlates of restless legs syndrome in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31:1078–1083.

7. Schormair B, Kemlink D, Roeske D, Eckstein G, Xiong L, Lichtner P, et al. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet. 2008; 40:946–948.

8. Yang Q, Li L, Chen Q, Foldvary-Schaefer N, Ondo WG, Wang QK. Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population. Sleep Med. 2011; 12:800–804.

9. Kang SG, Lee HJ, Choi JE, Park JH, Lee SS, Han CS, et al. Possible association between G-protein β3 subunit C825T polymorphism and antipsychotic-induced restless legs syndrome in schizophrenia. Acta Neuropsychiatrica. 2007; 19:351–356.

10. Kang SG, Lee HJ, Choi JE, Park YM, Park JH, Han C, et al. Association study between antipsychoticsinduced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia. Neuropsychobiology. 2008; 57:49–54.

11. Cho CH, Kang SG, Choi JE, Park YM, Lee HJ, Kim L. Association between Antipsychotics-Induced Restless Legs Syndrome and Tyrosine Hydroxylase Gene Polymorphism. Psychiatry Investig. 2009; 6:211–215.

12. Kang SG, Park YM, Choi JE, Lim SW, Lee HJ, Lee SH, et al. Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia. Hum Psychopharmacol. 2010; 25:397–403.

13. Kang SG, Lee HJ, Park YM, Yang HJ, Song HM, Lee YJ, et al. The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia. Hum Psychopharmacol. 2013; 28:117–123.

14. Jung JS, Cho CH, Yoon HK, Kang SG, Park YM, Lee HJ, Kim L. Association between Antipsychotic-Related Restless Legs Syndrome and the RORA Gene Polymorphism in Schizophrenia. Korean J Schizophr Res. 2013; 16:93–97.

15. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003; 4:121–132.

16. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res. 2003; 55:263–267.

17. Lykke J, Hesse M, Austin SF, Oestrich I. Validity of the BPRS, the BDI and the BAI in dual diagnosis patients. Addict Behav. 2008; 33:292–300.

18. Uetani N, Chagnon MJ, Kennedy TE, Iwakura Y, Tremblay ML. Mammalian motoneuron axon targeting requires receptor protein tyrosine phosphatases sigma and delta. J Neurosci. 2006; 26:5872–5880.

19. Pulido R, Krueger NX, Serra-Pagès C, Saito H, Streuli M. Molecular characterization of the human transmembrane protein-tyrosine phosphatase delta. Evidence for tissue-specific expression of alternative human transmembrane protein-tyrosine phosphatase delta isoforms. J Biol Chem. 1995; 270:6722–6728.

20. Sato M, Takahashi K, Nagayama K, Arai Y, Ito N, Okada M, et al. Identification of chromosome arm 9p as the most frequent target of homozygous deletions in lung cancer. Genes Chromosomes Cancer. 2005; 44:405–414.

21. Lin CH, Chen ML, Wu VC, Li WY, Sy HN, Wu SL, et al. Association of candidate genetic variants with restless legs syndrome in end stage renal disease: a multicenter case-control study in Taiwan. Eur J Neurol. 2014; 21:492–498.