Abstract
We earlier found an association between anorexia nervosa (AN) restrictive subtype (AN-R) and an inserted sequence within the NETpPR, a polymorphic region located in the promoter of the solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 (SLC6A2) gene. To further examine the noradrenergic system in AN-R we performed an association study with a functional polymorphism (MAOA-uVNTR) in the promoter of the monoamine oxidase A (MAOA) gene. Since monoamine oxidase A metabolises noradrenalin, a positive association with the MAOA gene would be biologically plausible. The transmission disequilibrium test and 95 trios/duos (AN-R females+biological parents) showed the main effect of the longer, more transcriptionally active form of the MAOA-uVNTR (MAOA-L) to be statistically non-significant (McNemar's χ2=1.4, df=1, P=0.238, odds ratio: 1.4, 95% CI 0.8–2.7). A case–control approach supported this finding. We then stratified the MAOA-uVNTR TDT data according to the (a) NETpPR genotype of the AN-R females, and (b) NETpPR allele transmitted from NETpPR-S4/L4 heterozygous mothers. In both cases, contingency table analysis revealed previously unreported gene-gene interaction between the MAOA and SLC6A2 genes (P=0.019 and 0.019, respectively). Receiving an MAOA-L allele more than doubles the risk for developing AN-R, conditional on an individual also being a NETpPR-L4 homozygote (stratum-specific odds ratio: 2.4, 95% CI 1.1–6.0). These results suggest important involvement of the noradrenergic system in the biological underpinnings of AN-R.
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Acknowledgements
This study was supported by the Children's Hospital Fund Small grant SGS9808 and donations from the Estate of the Late Charlotte Ross and from Anne Shaw Kennedy. We thank Prof Derek Gordon from the Laboratory of Statistical Genetics, Rockefeller University, USA, for statistical advice and are grateful to Drs Wiley and Carpenter at The Children's Hospital at Westmead for the use of their laboratories. We appreciate the recruitment of study participants at ‘Footprints of Angels’, Northside Clinic, Royal Prince Alfred Hospital, The Children's Hospital at Westmead, Wesley Private Hospital, and Westmead Hospital. We specially thank the families for participating.
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Urwin, R., Bennetts, B., Wilcken, B. et al. Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype). Eur J Hum Genet 11, 945–950 (2003). https://doi.org/10.1038/sj.ejhg.5201077
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DOI: https://doi.org/10.1038/sj.ejhg.5201077
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