Weight-restored patients with anorexia nervosa (AN) respond favorably to the 
selective serotonin reuptake inhibitor fluoxetine, which justifies association 
studies of the serotonin transporter gene (SLC6A4, alias SERT) and AN. 
Case-control studies suggest that the least transcriptionally active allele of 
the SERT gene promoter polymorphism (5-HTTLPR) has an increased frequency in AN 
patients. However, this finding was not replicated with 55 trios (AN 
child+parents) and the transmission disequilibrium test (TDT). To clarify the 
role of the 5-HTTLPR in susceptibility to AN, we used the TDT and 106 Australian 
trios to provide 93% power to detect a genotypic relative risk (GRR) of 2.0. Our 
results were negative for this GRR (McNemar's chi(2)=0.01, df=1, p=0.921, odds 
ratio 1.0, 95% CI 0.7-1.5). Additionally, we found no association with AN 
females, AN subtype, age at onset, or minimum BMI. We then performed the first 
reported investigation of epistasis between the SERT gene and norepinephrine 
transporter gene (SLC6A2, alias NET) in AN, as an earlier study suggested that 
atypical AN responds to the dual serotonin-norepinephrine reuptake inhibitor 
venlafaxine. We observed no epistasis between the 5-HTTLPR and a polymorphism 
within the NET gene promoter polymorphic region (NETpPR) (chi(2)=0.48, df=1, 
p=0.490). Although 5-HTTLPR modulates serotonin reuptake by the serotonin 
transporter, our analyses provide no evidence that susceptibility to AN is 
modified by 5-HTTLPR alone, nor in concert with as yet undetermined functional 
effects of the NETpPR polymorphism.