Skip to main content
SpringerLink
Log in

That’s not it, either-neither polymorphisms in PHOX2B nor in MIF are involved in sudden infant death syndrome (SIDS)

  • Short Communication
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

The occurrence of sudden infant death syndrome (SIDS) has been linked to several genetic risk factors, e.g. genes involved in the neuroadrenergic system, variations in serotonin reporter genes or mutations in long-QT syndrome genes. Additionally, polymorphisms in genes with impact in sleep disorder syndromes have been proposed to be of importance as genetic risk factors for SIDS. In this study, we investigated the polyalanine length variation of PHOX2B and the −794 CATT repeat in the MIF promoter region as well as single nucleotide polymorphisms (rs28462174, rs28727473, rs16853571, rs755622, rs12485058, rs12485068, rs4822444, rs4822445, rs4822446, rs4822447 and rs2012124) in both genes in 278 SIDS cases and 240 controls. No significant differences were found in allele distribution of neither length polymorphisms nor single nucleotide polymorphisms between SIDS cases or controls. Therefore, an importance of these variations for the occurrence of SIDS could be ruled out.

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

References

  1. Krous FK, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, Cutz E, Hanzlick R, Keens TG, Mitchell EA (2004) Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114:234–238

    Article  PubMed  Google Scholar 

  2. Thach BT (2005) The role of respiratory control disorders in SIDS. Respir Physiol Neurobiol 149:343–353

    Article  PubMed  Google Scholar 

  3. Doi A, Ramirez JM (2008) Neuromodulation and the orchestration of the respiratory rhythm. Respir Physiol Neurobiol 164:96–104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Kinney HC, Richerson GB, Dymecki SM, Darnall RA, Nattie EE (2009) The brainstem and serotonin in the sudden infant death syndrome. Annu Rev Pathol 4:517–550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Blair PS, Sidebotham P, Evason-Coombe C, Edmonds M, Heckstall-Smith EM, Fleming P (2009) Hazardous cosleeping environments and risk factors amenable to change: case–control study of SIDS in south west England. BMJ 339:b3666

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kinney HC, Thach BT (2009) Medical progress: the sudden infant death syndrome. N Engl J Med 361:795–805

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, Towbin JA (2001) Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 286:2264–2269

    Article  CAS  PubMed  Google Scholar 

  8. Wedekind H, Bajanowski T, Friederich P, Breithardt G, Wülfing T, Siebrans C, Engeland B, Mönnig G, Haverkamp W, Brinkmann B, Schulze-Bahr E (2006) Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study. Int J Legal Med 120:129–137

    Article  PubMed  Google Scholar 

  9. Opdal SH, Vege A, Rognum TO (2008) Serotonin transporter gene variation in sudden infant death syndrome. Acta Paediatr 97:861–865

    Article  CAS  PubMed  Google Scholar 

  10. Klintschar M, Reichenpfader B, Saternus KS (2008) A functional polymorphism in the tyrosine hydroxylase gene indicates a role of noradrenalinergic signaling in sudden infant death syndrome. J Pediatr 153:190–193

    Article  CAS  PubMed  Google Scholar 

  11. Rand CM, Patwari PP, Carroll MS, Weese-Mayer DE (2013) Congenital central hypoventilation syndrome and sudden infant death syndrome: disorders of autonomic regulation. Semin Pediatr Neurol 20:44–55

    Article  PubMed  Google Scholar 

  12. Läer K, Vennemann M, Rothämel T, Klintschar M (2013) Association between polymorphisms in the P2RY1 and SSTR2 genes and sudden infant death syndrome. Int J Legal Med 127:1087–1091

    Article  PubMed  Google Scholar 

  13. Lavezzi AM, Casale V, Oneda R, Gioventu S, Matturri L, Farronato G (2013) Obstructive sleep apnea syndrome (OSAS) in children with class III malocclusion: involvement of the PHOX2B gene. Sleep Breath 17:1275–1280

    Article  PubMed  Google Scholar 

  14. Khalyfa A, Kheinrandish-Gozal L, Capdevila OS, Bhattacharjee R, Gozal D (2012) Macrophage migration inhibitory factor gene polymorphisms and plasma levels in children with obstructive sleep apnea. Pediatr Pulmonol 47:1001–1011

    Article  PubMed Central  PubMed  Google Scholar 

  15. Edwards KM, Tomfohr LM, Mills PF, Bosch JA, Ancoli-Israel S, Loredo JS, Dimsdale J (2011) Macrophage migratory inhibitory factor (MIF) may be a key factor in inflammation in obstructive sleep apnea. Sleep 34:161–163

    PubMed Central  PubMed  Google Scholar 

  16. Gronli JO, Santucci BA, Leurgans SE, Berry-Kravis EM, Weese-Mayer DE (2008) Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatr Pulmonol 43:77–86

    Article  PubMed  Google Scholar 

  17. Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Mannam P, Allore H, Fried T, Bucala R, Lee PJ (2014) Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 306:L487–L496

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. De la Cruz-Mosso U, Bucala R, Palafox-Sanchez CA, Parra-Rojas I, Padilla-Gutierrez JR, Pereira-Suarez AL, Rangel-Villalobos H, Vazquez-Villamar M, Angel-Chavez LI, Munoz-Valle JF (2014) Macrophage migration inhibitory factor: association of −794 CATT5–8 and −173 G > C polymorphisms with TNF-α in systemic lupus erythematosus. Hum Immunol 75:433–439

    Article  PubMed Central  PubMed  Google Scholar 

  19. Denkinger CM, Metz C, Fingerle-Rowson G, Denkinger MD, Forsthuber T (2004) Macrophage migration inhibitory factor and its role in autoimmune diseases. Arch Immunol Ther Exp (Warsz) 52:389–400

    CAS  Google Scholar 

  20. Liebrechts-Akkerman F, Liu F, Lao O, Ooms AH, van Duijn K, Vermeulen M, Jaddoe VW, Hofman A, Engelberts AC, Kayser M (2014) PHOX2B polyalanine repeat length is associated with sudden infant death syndrome and unclassified sudden infant death in the Dutch population. Int J Legal Med 128:621–629

    PubMed  Google Scholar 

  21. Opdal SH, Vege A, Rognum TO (2014) Genetic variation in the monoamine oxidase A and serotonin transporter genes in sudden infant death syndrome. Acta Paediatr 103:393–397

    Article  CAS  PubMed  Google Scholar 

  22. Studer J, Bartsch C, Haas C (2014) Sodium/proton exchanger 3 (NHE3) and sudden infant death syndrome (SIDS). Int J Legal Med 128:939–943

    Article  PubMed  Google Scholar 

  23. Opdal SH, Rognum TO (2007) The IL6-174G/C polymorphism and sudden infant death syndrome. Hum Immunol 68:541–543

    Article  CAS  PubMed  Google Scholar 

  24. Groß M, Bajanowski T, Vennemann M, Poetsch M (2014) Sudden infant death syndrome (SIDS) and polymorphisms in monoamine oxidase A gene (MAOA): a revisit. Int J Legal Med 128:43–49

    Article  PubMed  Google Scholar 

  25. Findeisen M, Vennemann M, Brinkmann B, Ortmann C, Röse I, Köpcke W, Jorch G, Bajanowski T (2003) German study on sudden infant death (GeSID): design, epidemiological and pathological profile. Int J Legal Med 118:163–169

    Google Scholar 

  26. Bajanowski T, Brinkmann B, Vennemann M (2006) The San Diego definition of SIDS: practical application and comparison with the GeSID classification. Int J Legal Med 120:331–336

    Article  CAS  PubMed  Google Scholar 

  27. Vennemann MT, Findeisen M, Bajanowski T, Butterfaß-Bahloul T, Jorch G, Brinkmann B et al (2005) Modifiable risk factors for SIDS in Germany, results of GeSID. Acta Paediatr 94:655–660

    Article  PubMed  Google Scholar 

  28. Chen QS, Wang W, Lin PX, Zhong QH, Yu SY, Nan Fang, Yi Ke, Da Xue, Xue Bao (2009) Application of Excel programs of Fisher exact probability test for medical data. 29:791–793

  29. Excoffier L, Laval G, Schneider S (2005) Arlequin ver. 3.0: an integrated software package for population genetics data analysis. Evol Bioinformatics Online 1:47–50

    CAS  Google Scholar 

  30. Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Rand CM (2008) Congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS): kindred disorders. Respir Physiol Neurobiol 164:38–48

    Article  CAS  PubMed  Google Scholar 

  31. Amiel J, Laudier B, Attié-Bitach T, Trang H, de Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyonnet S (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33:459–461

    Article  CAS  PubMed  Google Scholar 

  32. Dubreuil V, Ramanantsoa N, Trochet D, Vaubourg V, Amiel J, Gallego J, Brunet JF, Goridis C (2008) A human mutation in Phox2b causes lack of CO2 chemosensitivity, fetal central apnea, and specific loss of parafacial neurons. Proc Natl Acad Sci U S A 105:1067–1072

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Lavezzi AM, Weese-Mayer DE, Yu MY, Jennings LJ, Corna MF, Casale V, Oneda R, Matturri L (2012) Developmental alterations of the respiratory human retrotrapezoid nucleus in sudden unexplained fetal and infant death. Auton Neurosci 170:12–19

    Article  CAS  PubMed  Google Scholar 

  34. Rand CM, Weese-Mayer DE, Zhou L, Maher BS, Cooper ME, Marazita ML, Berry-Kravis EM (2006) Sudden infant death syndrome: case–control frequency differences in paired like homeobox (PHOX) 2B gene. Am J Med Genet A 140:1687–1691

    Article  PubMed  Google Scholar 

  35. Kijima K, Sasaki A, Niki T, Umetsu K, Osawa M, Matoba R, Hayasaka K (2004) Sudden infant death syndrome is not associated with the mutation of PHOX2B gene, a major causative gene of congenital central hypoventilation syndrome. Tohoku J Exp Med 203:65–68

    Article  CAS  PubMed  Google Scholar 

  36. Wang FF, Huang XF, Shen N, Leng L, Bucala R, Chen SL, Lu LJ (2013) A genetic role for macrophage migration inhibitory factor (MIF) in adult-onset Still’s disease. Arthritis Res Ther 15:R65

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Valdes-Alvarado E, Munoz-Valle JF, Valle Y, Sandoval-Pinto E, Garcia-Gonzalez IJ, Valdez-Haro A, De la Cruz-Mosso U, Flores-Salinas HE, Padilla-Gutierrez JR (2014) Association between the −794(CAAT)5–8 MIF gene polymorphism and susceptibility to acute coronary syndrome in a western Mexican population. J Immunol Res 2014:704854

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Compliance with ethical standards

The German SIDS study providing the SIDS cases was funded by the German Ministry of Education, Science, Research and Technology (grant number 01ED9401). All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Institute of Legal Medicine, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany

    Micaela Poetsch, Rebecca Todt & Thomas Bajanowski

  2. Institute of Legal Medicine, University of Münster, Münster, Germany

    Mechtild Vennemann

Authors
  1. Micaela Poetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Todt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mechtild Vennemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Bajanowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Micaela Poetsch.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table S1

SNP primer sequences and concentrations (DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Poetsch, M., Todt, R., Vennemann, M. et al. That’s not it, either-neither polymorphisms in PHOX2B nor in MIF are involved in sudden infant death syndrome (SIDS). Int J Legal Med 129, 985–989 (2015). https://doi.org/10.1007/s00414-015-1213-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-015-1213-3

Keywords

Search

Navigation