Skip to main content

Advertisement

SpringerLink
Log in

Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population

  • Sleep Breathing Physiology and Disorders • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Background

Parkinson’s disease (PD) and restless legs syndrome/Willis-Ekbom disease (RLS/WED) are both common movement disorders. Based on their clinical overlap, association studies of PD and RLS/WED have been conducted for many years.

Objective

To investigate whether or not the genetic risk factor of PD was also associated with RLS/WED.

Subjects and methods

We included 102 idiopathic RLS/WED patients and 189 matched controls from southeast China. The clinical data included the International Restless Legs Syndrome Study Group Rating Scale, the subtypes of RLS/WED symptoms (painful or other discomfort), the comorbidities, the pregnancy history of female patients, the Hamilton Depression Scale (HAMD), and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Risk gene analysis between RLS/WED and control groups including 21 SNPs (single nucleotide polymorphisms) was conducted. Genotyping was done by Sanger sequencing.

Results

We found that rs4273468 polymorphism of BST1 gene increased the risk of idiopathic RLS/WED patients in southeastern Chinese population (P = <0.001, OR = 2.85, p = 0.019 after Bonferroni correction). Moreover, the haplotype of G-G (rs4698412-rs4273468) was significantly associated with Chinese RLS/WED patients (p = <0.001).

Conclusion

BST1 may contribute to the development of RLS/WED. Further studies on larger cohorts are needed to confirm these findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CI:

confidence interval

GWAS:

genome-wide association study

HWE:

Hardy-Weinberg equilibrium

OR:

odds ratio

SNPs:

single nucleotide polymorphisms

RLS:

restless legs syndrome

PD:

Parkinson’s disease

IRLSSG:

International Restless Legs Syndrome Study Group

HAMD:

Hamilton Depression Scale

PSQI:

Pittsburgh Sleep Quality Index

IRLSSG rating scales:

International Restless Legs Syndrome Study Group Rating Scale

References

  1. Krishnan PR, Bhatia M, Behari M (2003) Restless legs syndrome in Parkinson’s disease: a case-controlled study. Mov Disord 18:181–185

    Article  Google Scholar 

  2. Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K (2006) Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson’s disease. Mov Disord 21:380–384

    Article  Google Scholar 

  3. Walters AS, LeBrocq C, Passi V, Patel S, Hanna PA, Cohen B, Wagner M (2003) A preliminary look at the percentage of patients with restless legs syndrome who also have Parkinson disease, essential tremor or Tourette syndrome in a single practice. J Sleep Res 12:343–345

    Article  Google Scholar 

  4. Wong JC, Li Y, Schwarzschild MA, Ascherio A, Gao X (2014) Restless legs syndrome: an early clinical feature of Parkinson disease in men. Sleep 37:369–372

    Article  Google Scholar 

  5. Alonso-Navarro H, García-Martín E, Agúndez JAG, Jiménez-Jiménez FJ (2019) Association between restless legs syndrome and other movement disorders. Neurology 92:948–964

    Article  Google Scholar 

  6. Calzetti S, Angelini M, Negrotti A, Marchesi E, Goldoni M (2014) A long-term prospective follow-up study of incident RLS in the course of chronic DAergic therapy in newly diagnosed untreated patients with Parkinson’s disease. J Neural Transm (Vienna) 121:499–506

    Article  CAS  Google Scholar 

  7. Marchesi E, Negrotti A, Angelini M, Goldoni M, Abrignani G, Calzetti S (2016) A prospective study of the cumulative incidence and course of restless legs syndrome in de novo patients with Parkinson’s disease during chronic dopaminergic therapy. J Neurol 263:441–447

    Article  Google Scholar 

  8. Gan-Or Z, Alcalay RN, Bar-Shira A, Leblond CS, Postuma RB, Ben-Shachar S, Waters C, Johnson A, Levy O, Mirelman A, Gana-Weisz M, Dupré N, Montplaisir J, Giladi N, Fahn S, Xiong L, Dion PA, Orr-Urtreger A, Rouleau GA (2015) Genetic markers of restless legs syndrome in Parkinson disease. Parkinsonism Relat Disord 21:582–585

    Article  Google Scholar 

  9. Mohtashami S, He Q, Ruskey JA, Zhou S, Dion PA, Allen RP, Earley CJ, Fon EA, Xiong L, Dupre N, Dauvilliers Y, Rouleau GA, Gan-Or Z (2018) TOX3 variants are involved in restless legs syndrome and Parkinson’s disease with opposite effects. J Mol Neurosci 64:341–345

    Article  CAS  Google Scholar 

  10. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study Group (2014) Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 15:860–873

    Article  Google Scholar 

  11. García-Borreguero D, Allen RP, Kohnen R, Högl B, Trenkwalder C, Oertel W, Hening WA, Paulus W, Rye D, Walters A, Winkelmann J, Earley CJ, International Restless Legs Syndrome Study Group (2007) Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute. Sleep Med 8:520–530

    Article  Google Scholar 

  12. Ahmad NN, Cu-Unjieng AB, Donoso LA (1995) Modification of standard proteinase K/phenol method for DNA isolation to improve yield and purity from frozen blood. J Med Genet 32:129–130

    Article  CAS  Google Scholar 

  13. Guo JF, Li K, Yu RL et al (2015) Polygenic determinants of Parkinson’s disease in a Chinese population. Neurobiol Aging 36:1765.e1761–1765.e1766

    Google Scholar 

  14. Yokoyama S, Al Mahmuda N, Munesue T et al (2015) Association study between the CD157/BST1 gene and autism spectrum disorders in a Japanese population. Brain Sci 5:188–200

    Article  CAS  Google Scholar 

  15. D’Souza T, Rajkumar AP (2020) Systematic review of genetic variants associated with cognitive impairment and depressive symptoms in Parkinson’s disease. Acta Neuropsychiatr 32:10–22

    Article  Google Scholar 

  16. Yuan L, Song Z, Deng X, Xiong W, Yang Z, Deng H (2016) Association of the MTHFR rs1801131 and rs1801133 variants in sporadic Parkinson’s disease patients. Neurosci Lett 616:26–31

    Article  CAS  Google Scholar 

  17. Khaligh A, Goudarzian M, Moslem A, Mehrtash A, Jamshidi J, Darvish H, Emamalizadeh B (2017) RAB7L1 promoter polymorphism and risk of Parkinson’s disease; a case-control study. Neurol Res 39:468–471

    Article  CAS  Google Scholar 

  18. Wang L, Cheng L, Lu ZJ, Sun XY, Li JY, Peng R (2016) Association of three candidate genetic variants in RAB7L1/NUCKS1, MCCC1 and STK39 with sporadic Parkinson’s disease in Han Chinese. J Neural Transm (Vienna) 123:425–430

    Article  CAS  Google Scholar 

  19. Zhu XC, Cao L, Tan MS, Jiang T, Wang HF, Lu H, Tan CC, Zhang W, Tan L, Yu JT (2017) Association of Parkinson’s disease GWAS-linked loci with Alzheimer’s disease in Han Chinese. Mol Neurobiol 54:308–318

    Article  CAS  Google Scholar 

  20. Cheng L, Wang L, Li NN, Yu WJ, Sun XY, Li JY, Zhou D, Peng R (2016) SNCA rs356182 variant increases risk of sporadic Parkinson’s disease in ethnic Chinese. J Neurol Sci 368:231–234

    Article  CAS  Google Scholar 

  21. Hou B, Zhang X, Liu Z, Wang J, Xie A (2019) Association of rs356219 and rs3822086 polymorphisms with the risk of Parkinson’s disease: a meta-analysis. Neurosci Lett 709:134380

    Article  CAS  Google Scholar 

  22. Tan EK, Peng R, Teo YY, Tan LC, Angeles D, Ho P, Chen ML, Lin CH, Mao XY, Chang XL, Prakash KM, Liu JJ, Au WL, le WD, Jankovic J, Burgunder JM, Zhao Y, Wu RM (2010) Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study. Hum Mutat 31:561–568

    CAS  PubMed  Google Scholar 

  23. Refenes N, Bolbrinker J, Tagaris G, Orlacchio A, Drakoulis N, Kreutz R (2009) Role of the H1 haplotype of microtubule-associated protein tau (MAPT) gene in Greek patients with Parkinson’s disease. BMC Neurol 9:26

    Article  Google Scholar 

  24. Chang D, Nalls MA, Hallgrímsdóttir IB et al (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet 49:1511–1516

    Article  CAS  Google Scholar 

  25. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T (2007) Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39:1000–1006

    Article  CAS  Google Scholar 

  26. Peeraully T, Tan EK (2012) Genetic variants in sporadic Parkinson’s disease: East vs West. Parkinsonism Relat Disord 18(Suppl 1):S63–S65

    Article  Google Scholar 

  27. Higashida H, Hashii M, Tanaka Y, Matsukawa S, Higuchi Y, Gabata R, Tsubomoto M, Seishima N, Teramachi M, Kamijima T, Hattori T, Hori O, Tsuji C, Cherepanov SM, Shabalova AA, Gerasimenko M, Minami K, Yokoyama S, Munesue SI, Harashima A, Yamamoto Y, Salmina AB, Lopatina O (2019) CD38, CD157, and RAGE as molecular determinants for social behavior. Cells 9

  28. Schormair B, Zhao C, Bell S, Tilch E, Salminen AV, Pütz B, Dauvilliers Y, Stefani A, Högl B, Poewe W, Kemlink D, Sonka K, Bachmann CG, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek Z, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Allen RP, Earley CJ, Ondo WG, Xiong L, Montplaisir J, Gan-Or Z, Perola M, Vodicka P, Dina C, Franke A, Tittmann L, Stewart AFR, Shah SH, Gieger C, Peters A, Rouleau GA, Berger K, Oexle K, di Angelantonio E, Hinds DA, Müller-Myhsok B, Winkelmann J, Balkau B, Ducimetière P, Eschwège E, Rancière F, Alhenc-Gelas F, Gallois Y, Girault A, Fumeron F, Marre M, Roussel R, Bonnet F, Bonnefond A, Cauchi S, Froguel P, Cogneau J, Born C, Caces E, Cailleau M, Lantieri O, Moreau JG, Rakotozafy F, Tichet J, Vol S, Agee M, Alipanahi B, Auton A, Bell RK, Bryc K, Elson SL, Fontanillas P, Furlotte NA, Hinds DA, Hromatka BS, Huber KE, Kleinman A, Litterman NK, McIntyre MH, Mountain JL, Northover CAM, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Tung JY, Vacic V, Wilson CH (2017) Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol 16:898–907

    Article  Google Scholar 

  29. Lopatina O, Yoshihara T, Nishimura T et al (2014) Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease. Front Behav Neurosci 8:133

    Article  Google Scholar 

  30. Blauwendraat C, Nalls MA, Singleton AB (2020) The genetic architecture of Parkinson’s disease. Lancet Neurol 19:170–178

    Article  CAS  Google Scholar 

  31. Kelada SN, Checkoway H, Kardia SL et al (2006) 5′ and 3′ region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson’s disease risk: a hypothesis-generating study. Hum Mol Genet 15:3055–3062

    Article  CAS  Google Scholar 

  32. Wu YR, Feng IH, Lyu RK et al (2007) Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 144b:300–304

    Article  CAS  Google Scholar 

  33. Elbaz A, Levecque C, Clavel J, Vidal JS, Richard F, Amouyel P, Alpérovitch A, Chartier-Harlin MC, Tzourio C (2004) CYP2D6 polymorphism, pesticide exposure, and Parkinson’s disease. Ann Neurol 55:430–434

    Article  CAS  Google Scholar 

  34. Allen AS, Satten GA (2010) SNPs in CAST are associated with Parkinson disease: a confirmation study. Am J Med Genet B Neuropsychiatr Genet 153b:973–979

    CAS  PubMed  Google Scholar 

  35. Do CB, Tung JY, Dorfman E, Kiefer AK, Drabant EM, Francke U, Mountain JL, Goldman SM, Tanner CM, Langston JW, Wojcicki A, Eriksson N (2011) Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet 7:e1002141

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all the participants who contribute to this study.

Copyright

The International Parkinson and Movement Disorder Society will hold copyright to all published articles.

Funding

This work was supported by the National Natural Science Foundation of China (81571103) and the National Key R&D Program of China (2016YFC1306000). These fundings contributed to the design of the study, data collection, and in writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Neurology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, 200025, China

    Yumeng Huang, Pei Wang, Qi Luo & Jianfang Ma

Authors
  1. Yumeng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianfang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JM proposed the conception, diagnosed and collected restless legs patient clinical data. YH and PW conducted questionnaire evaluation and follow-up in restless legs patients and control group. YH performed genetic investigations, statistical analysis, and manuscript writing. JM performed review and critique of the manuscript.

Corresponding author

Correspondence to Jianfang Ma.

Ethics declarations

Ethics approval and consent to participate

The study was approved by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. All patients and health participants in the study gave written informed consent prior to obtaining the data.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Y., Wang, P., Luo, Q. et al. Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population. Sleep Breath 25, 1987–1993 (2021). https://doi.org/10.1007/s11325-021-02326-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-021-02326-y

Keywords

Search

Navigation