The Journal of Pediatrics
Volume 156, Issue 1 , Pages 44-48.e1 , January 2010

Impact of Sodium/Proton Exchanger 3 Gene Variants on Sudden Infant Death Syndrome

  • Micaela Poetsch, PhD

      Affiliations

    • Institute of Forensic Medicine, University Hospital Essen, Essen, Germany
    • Corresponding Author InformationReprint requests: Dr Micaela Poetsch, Institute of Forensic Medicine, University Hospital Essen, Hufelandstr. 55, D-45122 Essen, Germany.
  • ,
  • Bente J. Nottebaum, MD

      Affiliations

    • Institute of Forensic Medicine, University Hospital Essen, Essen, Germany
  • ,
  • Lisa Wingenfeld, MD

      Affiliations

    • Institute of Forensic Medicine, University Hospital Essen, Essen, Germany
  • ,
  • Stilla Frede, PhD

      Affiliations

    • Institute of Physiology, University Hospital Essen, Essen, Germany
  • ,
  • Mechtild Vennemann, PhD

      Affiliations

    • Institute of Legal Medicine, University of Münster, Münster, Germany
  • ,
  • Thomas Bajanowski, PhD

      Affiliations

    • Institute of Forensic Medicine, University Hospital Essen, Essen, Germany

Received 22 December 2008 ,Revised 21 May 2009 ,Accepted 7 July 2009.

References 

  1. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep. 2008;56:1–120
  2. Vennemann MT, Findeisen M, Bajanowski T, Butterfass-Bahloul T, Jorch G, Brinkmann B, et al. Modifiable risk factors for SIDS in Germany, results of GeSID. Acta Paediatr. 2005;94:655–660
  3. Carpenter RG, Irgens LM, Blair PS, England PD, Fleming P, Huber J, et al. Sudden unexplained infant death in 20 regions in Europe: case control study. Lancet. 2004;363:185–191
  4. Hauck FR, Moore CM, Herman SM, Donovan M, Kalelkar M, Christoffel KK, et al. The contribution of prone sleeping position to the racial disparity in sudden infant death syndrome: the Chicago Infant Mortality Study. Pediatrics. 2002;110:772–780
  5. Weese-Mayer D, Ackerman MJ, Marazita ML, Berry-Kravis EM. Sudden infant death syndrome: review of implicated genetic factors. Am J Med Genet A. 2007;143A:771–778
  6. Opdal SH, Rognum TO. The sudden infant death syndrome gene: does it exist.?. Pediatrics. 2004;114:e506–e512
  7. Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA. 2001;286:2264–2269
  8. Wedekind H, Bajanowski T, Friederich P, Breithardt G, Wülfing T, Siebrans C, et al. Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study. Int J Legal Med. 2006;120:129–137
  9. Klintschar M, Reichenpfader B, Saternus K- S. A functional polymorphism in the tyrosine hydrosylase gene indicates a role of noradrenalinergic signaling in sudden infant death syndrome. J Pediatr. 2008;153:190–193
  10. Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Curran ME, Silvestri JM, et al. Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development. Pediatr Res. 2004;56:391–395
  11. Hunt CE. Gene–environment interactions: implications for sudden unexpected deaths in infancy. Arch Dis Child. 2005;90:48–53
  12. Thach BT. The role of respiratory control disorders in SIDS. Respir Physiol Neurobiol. 2005;149:343–353
  13. Putnam RW, Filosa JA, Ritucci NA. Cellular mechanisms involved in CO2 and acid signalling in chemosensitive neurons. Am J Physiol Cell Physiol. 2004;287:C1493–C1526
  14. Crosby A, Robbins PA. Variability in end-tidal PCO2 and blood gas values in humans. Exp Physiol. 2003;88:603–610
  15. Orlowski J, Grinstein S. Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pflugers Arch. 2004;447:549–565
  16. Biemesderfer D, Pizzonia J, Abu-Alfa A, Exner M, Reilly R, Igarashi P, et al. NHE3: a Na/H exchanger isoform of renal brush border. Am J Physiol. 1993;265:F736–F742
  17. Bookstein C, DePaoli AM, Xie Y, Niu P, Musch MW, Rao MC, et al. Na_/H_ exchangers, NHE-1 and NHE-3, of rat intestine: expression and localization. J Clin Invest. 1994;93:106–113
  18. Brant SR, Yun CH, Donowitz M, Tse CM. Cloning, tissue distribution, and functional analysis of the human Na_/H_ exchanger isoform, NHE3. Am J Physiol. 1995;269:C198–C206
  19. Kiwull-Schöne H, Wiemann M, Frede S, Bingmann D, Wirth KJ, Heinelt U, et al. A novel inhibitor of the Na_/H_ echanger type 3 activates the central respiratory CO2 response and lowers the apneic threshold. Am J Respir Crit Care Med. 2001;164:1303–11
  20. Wiemann M, Frede S, Bingmann D, Kiwull P, Kiwull-Schöne H. Sodium/proton exchanges 3 in the medulla oblongata and set point of breathing control. Am J Respir Crit Care Med. 2005;172:244–249
  21. Wiemann M, Frede S, Tschentscher F, Kiwull-Schöne H, Kiwull P, Bingmann D, et al. NHE3 in the human brainstem: implications for the pathogenesis of the sudden infant death syndrome (SIDS)?. Adv Exp Med Biol. 2008;605:508–513
  22. Findeisen M, Vennemann M, Brinkmann B, Ortmann C, Röse I, Köpcke W, et al. German study on sudden infant death (GeSID): design, epidemiological and pathological profile. Int J Legal Med. 2004;118:163–169
  23. Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, et al. Sudden infant death syndrome (SIDS) and unclassified sudden infant deaths (USID): a definitional and diagnostic approach. Pediatrics. 2004;114:234–238
  24. Zhu H, Sagnella GA, Dong Y, Miler MA, Onipinla A, Markandu ND, et al. Molecular variants of the sodium/hydrogen exchanger type 3 gene and essential hypertension. J Hypertens. 2004;22:1269–1275
  25. Malakooti J, Memark VC, Dudeja PK, Ramaswamy K. Molecular cloning and functional analysis of the human Na+/H+ exchanger NHE3 promoter. Am J Physiol Gastrointest Liver Physiol. 2002;282:G491–G500
  26. Khoo MCK. Determinants of ventilatory instability and variability. Respir Physiol. 2000;122:167–182
  27. Dempsey JA, Smith CA, Przybylowski T, Chenuel B, Xie A, Nakayama H, et al. The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep. J Physiol. 2004;560:1–111
  28. Donowitz R, Li X. Regulatory binding partners and complexes of NHE3. Physiol Rev. 2007;87:825–872
  29. Levine SA, Nath SK, Yun CH, Yip JW, Montrose M, Donowitz M, et al. Separate COOH terminal domains of the epithelial specific brush border Na_/H_ exchanger isoform NHE3 are involved in stimulation and inhibition by protein kinases/growth factors. J Biol Chem. 1995;270:13716–13725
  30. Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, et al. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A. 1997;94:3010–3015
  31. Ribas-Salgueiro JL, Matarredona ER, Ribas J, Pásaro R. Enhanced c-Fos expression in the rostral ventral respiratory compülex and rostral oarapyramidal region by inhibition of the Na+/H+ exchanger type 3. Auton Neurosci. 2006;126-127:347–354
  32. Kiwull-Schöne H, Tepema L, Wiemann M, Kalhoff H, Kiwull P. Pharmacological im pact on loop gain properties to prevent irregular breathing. J Physiol Pharmacol. 2008;59:37–45
  33. Thach B. Tragic and sudden death. Potential and proven mechanisms causing sudden infant death syndrome. EMBO Rep. 2008;9:114–118

 Funded by a grant from the IFORES program run by the Duisburg-Essen University Medical School and the German Federal Ministry of Science and Education (1998 and 2003). The authors declare no conflicts of interest.

PII: S0022-3476(09)00651-9

doi: 10.1016/j.jpeds.2009.07.018

The Journal of Pediatrics
Volume 156, Issue 1 , Pages 44-48.e1 , January 2010