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Association of dopamine transporter and monoamine oxidase molecular polymorphisms with sudden infant death syndrome and stillbirth: new insights into the serotonin hypothesis

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Abstract

Recent findings demonstrated the role of neurotransmitters in the aetiopathogenesis of sudden unexpected deaths in infancy. Although genes involved in serotonin metabolism have been proposed as risk factors for sudden infant death syndrome (SIDS), the contribution of additional neurotransmitters and genes different from the serotonin transporter (SLC6A4, 5-HTT) has not been investigated. Considering the common metabolic pathway and synergism between dopamine and serotonin, the role of dopamine transporter (SLC6A3, DAT) and monoamine oxidase A (MAOA) genes in SIDS and stillbirth (sudden intrauterine unexplained death, SIUD) was investigated. Genotypes and allelic frequencies of DAT and MAOA were determined in 20 SIDS and five stillbirth cases and compared with 150 controls. No association was found between DAT polymorphisms and SIDS either at genotype (P = 0.64) or allelic (P = 0.86) level; however, a highly significant association was found between MAOA genotypes (P = 0.047) and alleles (P = 0.002) regulating different expression patterns (3R/3R vs 3.5R/3.5R + 4R/4R) in SIDS + SIUD and controls. Analysis of combined 5-HTTLPR (serotonin transporter linked polymorphic region)/MAOA genotypes revealed that frequency of L/L-4R/4R genotype combination was eightfold higher in SIDS + SIUD than in controls (P < 0.001). Findings are discussed considering the metabolic association among DAT, 5-HTT and MAOA with special emphasis on the linked action of 5-HTT/MAOA in regulating serotonin metabolism of SIDS and SIUD infants.

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Acknowledgements

The research was financed with an Emilia Romagna regional grant named “Modernization Project 2007”. The authors are thankful to the Italian association “Seeds for SIDS”, to Dr. Nicola Franchini (University of Parma) for collaboration in laboratory activities and to Dr. Simone Codeluppi neuroscientist at Burnham Institute for Medical Research (La Jolla) for critical reading of the manuscript. The investigation has been carried out in agreement with current national laws on scientific research in medical topics.

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Authors and Affiliations

  1. Department of Evolutionary and Functional Biology, University of Parma, Viale G.P. Usberti 11, 43100, Parma, Italy

    Laura Filonzi & Francesco Nonnis Marzano

  2. Department of Gynecology, Obstetrics and Neonatology, University of Parma, Via Gramsci, 43100, Parma, Italy

    Cinzia Magnani, Stefano Parmigiani & Giulio Bevilacqua

  3. “Lino Rossi” Research Center for the study and prevention of unexpected perinatal death and SIDS, University of Milan, Via della Commenda 19, 20122, Milan, Italy

    Anna Maria Lavezzi & Luigi Matturri

  4. Department of Pathology and Laboratory Medicine, University of Parma, Via Gramsci, 43100, Parma, Italy

    Guido Rindi

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  1. Laura Filonzi
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  2. Cinzia Magnani
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  3. Anna Maria Lavezzi
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  4. Guido Rindi
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  8. Francesco Nonnis Marzano
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Correspondence to Francesco Nonnis Marzano.

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Filonzi, L., Magnani, C., Lavezzi, A.M. et al. Association of dopamine transporter and monoamine oxidase molecular polymorphisms with sudden infant death syndrome and stillbirth: new insights into the serotonin hypothesis. Neurogenetics 10, 65–72 (2009). https://doi.org/10.1007/s10048-008-0149-x

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  • DOI: https://doi.org/10.1007/s10048-008-0149-x

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