No Correlation between AVPR1A Promoter Polymorphisms and Prepulse Inhibition in Patients with Nocturnal Enuresis

Sebastian Schulz-Juergensen, Philipp von Bismarck, René Santer, Paul Eggert

Department of General Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany.

DOI: 10.4236/ojneph.2014.41004                

Abstract

Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI and treatment with desamino arginine vasopressin (dDAVP), a ligand of the arginine vasopressin receptor 1A (AVPR1A), and both improve clanical symptoms and significantly increase PPI. Methods: In 17 children (median 9.1 years, range 6.4-17.3) with NE, promoter repeats within the RS1 and RS3 regions of AVPR1A were quantified and correlated to PPI (native and age-adjusted). Results: No direct correlation was found between the number of promoter repeats at RS1 and PPI (correlation coefficient—0.240, p = 0.346) or RS3 and PPI (correlation coefficient—0.0192, p = 0.936), with no change through age-adjustment of PPI. The different RS3 length subgroups did not show differences in PPI, nor did differentiation of NE according to clinical subtype or treatment response to dDAVP show differences in the number of promoter repeats. Conclusion: The missing reproducibility of the correlation between AVPR1A promoter polymorphisms and PPI in a group with wide range of PPI suggests a more complex interaction. Therefore, further investigations are needed to analyze this very plausible interaction. Conditions with a reduced PPI, such as enuresis, schizophrenia or autism, are particularly interesting for this research.

Keywords

AVPR1A Promoter; Prepulse Inhibition; Nocturnal Enuresis; Correlation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Naert, A., Callaerts-Vegh, Z. and D’Hooge, R. (2012) Nocturnal Hyperactivity, Increased Social Novelty Preference and Delayed Extinction of Fear Responses in Post-Weaning Socially Isolated Mice. Brain Research Bulletin, 85, 354-362. http://dx.doi.org/10.1016/j.brainresbull.2011.03.027
[2]	Giakoumaki, S.G. (2012) Cognitive and Prepulse Inhibition Deficits in Psychometrically High Schizotypal Subjects in the General Population: Relevance to Schizophrenia Research. Journal of the International Neuropsychological Society, 18, 643-656.
[3]	Semsar, K., Kandel, F.L. and Godwin, J. (2001) Manipulations of the AVT System Shift Social status and Related Courtship and Aggressive Behavior in the Bluehead Wrasse. Hormones and Behavior, 40, 21-31. http://dx.doi.org/10.1006/hbeh.2001.1663
[4]	Meyer-Lindenberg, A., Domes, G., Kirsch, P. and Heinrichs, M. (2011) Oxytocin and Vasopressin in the Human Brain: Social Neuropeptides for Translational Medicine. Nature Reviews Neuroscience, 12, 524-538. http://dx.doi.org/10.1038/nrn3044
[5]	Braff, D.L. and Geyer, M.A. (1990) Sensorimotor Gating and Schizophrenia. Human and Animal Model Studies. Archives of General Psychiatry, 47, 181-188. http://dx.doi.org/10.1001/archpsyc.1990.01810140081011
[6]	Parwani, A, Duncan, E.J., Bartlett, E., Madonick, S.H., Efferen, T.R., Rajan, R., Sanfilipo, M., Chappell, P.B., Chakravorty, S., Gonzenbach, S., Ko, G.N. and Rotrosen, J.P. (2000) Impaired Prepulse Inhibition of Acoustic Startle in Schizophrenia. Biological Psychiatry, 47, 662-669. http://dx.doi.org/10.1016/S0006-3223(99)00148-1
[7]	Perry, W., Minassian, A., Lopez, B., Maron, L. and Lincoln, A. (2007) Sensorimotor Gating Deficits in Adults with Autism. Biological Psychiatry, 61, 482-486. http://dx.doi.org/10.1016/j.biopsych.2005.09.025
[8]	Hammock, E.A. and Young, L.J. (2002) Variation in the Vasopressin V1a Receptor Promoter and Expression: Implications for Inter- and Intraspecific Variation in Social Behaviour. European Journal of Neuroscience, 16, 399-402. http://dx.doi.org/10.1046/j.1460-9568.2002.02083.x
[9]	Hopkins, W.D., Donaldson, Z.R. and Young, L.J. (2012) A Polymorphic Indel Containing the RS3 Microsatellite in the 5’ Flanking Region of the Vasopressin V1a Receptor Gene Is Associated with Chimpanzee (Pan troglodytes) Personality. Genes, Brain and Behavior, 11, 552-558. http://dx.doi.org/10.1111/j.1601-183X.2012.00799.x
[10]	Walum, H., Westberg, L., Henningsson, S., Neiderhiser, J.M., Reiss, D., Igl, W., Ganiban, J.M., Spotts, E.L., Pedersen, N.L., Eriksson, E. and Lichtenstein, P. (2008) Genetic Variation in the Vasopressin Receptor 1a Gene (AVPR1A) Associates with Pair-Bonding Behavior in Humans. Proceedings of the National Academy of Sciences, 105, 14153-14156. http://dx.doi.org/10.1073/pnas.0803081105
[11]	Levin, R., Heresco-Levy, U., Bachner-Melman, R, Israel, S., Shalev, I. and Ebstein, R.P. (2009) Association between Arginine Vasopressin 1a Receptor (AVPR1a) Promoter Region Polymorphisms and Prepulse Inhibition. Psychoneuroendocrinology, 34, 901-908. http://dx.doi.org/10.1016/j.psyneuen.2008.12.014
[12]	Ornitz, E.M., Russell, A.T., Hanna, G.L., Gabikian, P., Gehricke, J.G., Song, D. and Guthrie, D. (1999) Prepulse Inhibition of Startle and the Neurobiology of Primary Nocturnal Enuresis. Biological Psychiatry, 45, 1455-1466.
[13]	Baeyens, D., Roeyers, H., Naert, S., Hoebeke, P. and VandeWalle, J. (2007) The Impact of Maturation of Brainstem Inhibition on Enuresis: A Startle Eye Blink Modification Study with 2-Year Followup. Journal of Urology, 178, 2621-2625. http://dx.doi.org/10.1016/j.juro.2007.07.061
[14]	Schulz-Juergensen, S., Rieger, M., Schaefer, J., Neusuess, A. and Eggert, P. (2007) Effect of 1-Desamino-8-D-Arginine Vasopressin on Prepulse Inhibition of Startle Supports a Central Etiology of Primary Monosymptomatic Enuresis. Journal of Pediatrics, 151, 571-574. http://dx.doi.org/10.1016/j.jpeds.2007.05.024
[15]	Eggert, P., Freischmidt, S., Bismarck, P.V. andSchulz-Jürgensen, S. (2012) Differentiation of Treatment Options for Enuresis by Measurement of Prepulse Inhibition of Startle Reflex. Acta Paediatrica, 101, e304-e308.
[16]	Blumenthal, T.D., Cuthbert, B.N., Filion, D.L., Hackley, S., Lipp, O.V. and van Boxtel, A. (2005) Committee Report: Guidelines for Human Startle Eyeblinkelectromyographic Studies. Psychophysiology, 42, 1-15. http://dx.doi.org/10.1111/j.1469-8986.2005.00271.x
[17]	Gebhardt, J., Schulz-Juergensen, S. and Eggert, P. (2012) Maturation of Prepulse Inhibition (PPI) in Childhood. Psychophysiology, 49, 484-488. http://dx.doi.org/10.1111/j.1469-8986.2011.01323.x
[18]	Knafo, A., Israel, S., Darvasi, A., Bachner-Melman, R., Uzefovsky, F., Cohen, L., Feldman, E., Lerer, E., Laiba, E., Raz, Y., Nemanov, L., Gritsenko, I., Dina, C., Agam, G., Dean, B., Bornstein, G. and Ebstein, R.P. (2008) Individual Differences in Allocation of Funds in the Dictator Game Associated with Length of the Arginine Vasopressin 1a Receptor RS3 Promoter Region and Correlation between RS3 Length and Hippocampal mRNA. Genes, Brain and Behavior, 7, 266-275. http://dx.doi.org/10.1111/j.1601-183X.2007.00341.x
[19]	Frary, L.G. (1935) Enuresis: A Genetic Study. American Journal of Diseases in Children, 49, 557-578. http://dx.doi.org/10.1001/archpedi.1935.01970030003001
[20]	Hallgren, B. (1957) Enuresis: A Clinical and Genetic Study. Acta Psychiatrica et Neurologica Scandinavica, Supplementum, 114, 1-159.
[21]	Eiberg, H., Berendt, I. and Mohr, J. (1995) Assignment of Dominant Inherited Nocturnal Enuresis (ENUR1) to Chromosome 13q. Nature Genetics, 10, 354-356. http://dx.doi.org/10.1038/ng0795-354
[22]	Arnell, H., Hjälmås, K., Jägervall, M., Läckgren, G., Stenberg, A., Bengtsson, B., Wassén, C., Emahazion, T., Annerén, G., Pettersson, U., Sundvall, M. and Dahl, N. (1997) The Genetics of Primary Nocturnal Enuresis: Inheritance and Suggestion of a Second Major Gene on Chromosome 12q. Journal of Medical Genetics, 34, 360-365. http://dx.doi.org/10.1136/jmg.34.5.360
[23]	Eiberg, H. (1998) Total Genome Scan Analysis in a Single Extended Family for Primary Nocturnal Enuresis: Evidence for a New Locus (ENUR3) for Primary Nocturnal Enuresis on Chromosome 22q11. European Urology, 33, 34-36.
[24]	Thibonnier, M., Auzan, C., Madhun, Z., Wilkins, P., Berti-Mattera, L. and Clauser, E. (1994) Molecular Cloning, Sequencing, and Functional Expression of a cDNA Encoding the Human V1a Vasopressin Receptor. The Journal of Biological Chemistry, 269, 3304-3310.
[25]	Jonat, S., Santer, R., Schneppenheim, R., Obser, T. and Eggert, P. (1999) Effect of DDAVP on Nocturnal Enuresis in a Patient with Nephrogenic Diabetes Insipidus. Archives of Disease in Childhood, 81, 57-59. http://dx.doi.org/10.1136/adc.81.1.57
[26]	Robben, J.H., Sze, M., Knoers, N.V., Eggert, P., Deen, P. and Müller, D. (2007) Relief of Nocturnal Enuresis by Desmopressin Is Kidney and Vasopressin Type 2 Receptor Independent. Journal of the American Society of Nephrology, 18, 1534-1539.
[27]	Meir, J. and Eggert, P. (2011) Prepulse Inhibition of the Startle Reflex for the Differentiation of Enuresis in Children. Pediatric Nephrology, 26, 939-943.