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  • Original Research Article
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Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region

Molecular Psychiatry volume 7, pages 652–657 (2002)Cite this article

Abstract

Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls.1,2 Since this may reflect altered reuptake by the norepinephrine transporter (NET), we hypothesised that the NET gene was involved in the genetic component3 of AN. PCR-amplification of an AAGG repeat island (AAGG1) in the NET gene promoter region revealed a novel 343-bp sequence with five additional AAGG repeat islands (AAGG2–AAGG6). We named the sequence from AAGG1 to AAGG6 inclusive, the NET gene promoter polymorphic region (NETpPR). A 4-bp deletion (S4) or insertion (L4) in AAGG4 resulted in the net loss or gain, respectively, of a putative Elk-1 transcription factor site. The transmission disequilibrium test4(TDT) with 87 Australian trios (patient plus parents) demonstrated significant preferential transmission of L4 (McNemar's χ2 = 7.806, df = 1, P = 0.0052, odds ratio: 2.1) from parent to child with restricting AN (AN-R), suggesting that L4 or a DNA variant in linkage disequilibrium with it, doubles the risk for developing AN-R.

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Acknowledgements

This study was supported by the Children's Hospital Fund Small grant SGS9808, and donations from Anne Shaw Kennedy in remembrance of her son Jamie Ballestero, and the Estate of the Late Charlotte Ross. We are grateful to Drs Wiley and Carpenter for the use of their laboratories, and to those involved at ‘Footprints of Angels’, Northside Clinic, Royal Prince Alfred Hospital, The Children's Hospital at Westmead, Wesley Private Hospital, and Westmead Hospital for recruiting the study participants. We specially thank the young people and their families for making this study possible.

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Authors and Affiliations

  1. Department of Psychological Medicine, The Children's Hospital at Westmead, Westmead, NSW, Australia

    R E Urwin & K P Nunn

  2. Department of Molecular Genetics, The Children's Hospital at Westmead, Westmead, NSW, Australia

    B Bennetts

  3. Department of Biochemical Genetics & Newborn Screening, The Children's Hospital at Westmead, Westmead, NSW, Australia

    B Wilcken

  4. Adolescent Medical Unit, Westmead Hospital, Westmead, NSW, Australia

    B Lampropoulos & S Clarke

  5. Department of Psychiatry, Royal Prince Alfred Hospital, Camperdown, NSW, Australia

    P Beumont

  6. Department of Psychological Medicine, University of Sydney, Australia

    J Russell

  7. Wesley Private Hospital, Ashfield, NSW, Australia

    S Tanner

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Correspondence to R E Urwin.

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Urwin, R., Bennetts, B., Wilcken, B. et al. Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. Mol Psychiatry 7, 652–657 (2002). https://doi.org/10.1038/sj.mp.4001080

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