Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa

Abstract

Previous studies have demonstrated aberrant expression of serotonin in individuals with an eating disorder. Given this the serotonin transporter gene (5-HTT) is a strong candidate to contribute to the genetic component of the aetiology of eating disorders. To determine the role of this particular gene in the susceptibility to anorexia nervosa (AN) we have examined a tandemly repeated sequence close to the promotor region of the 5-HTT gene, which is represented by a long (L) and short (S) variant. Previous studies have shown that the transcriptional activity of the 5-HTT gene differs significantly between these two alleles. A group of 138 Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria AN patients and 90 controls were genotyped at the 5-HTT gene linked polymorphism (5-HTTLPR). Statistical analysis showed no significant difference in allele or genotype frequencies between the two groups. These data suggest that there is no association between 5-HTTLPR genotype and susceptibility to AN, in our population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:53-55, 2000.

Investigation of Epistasis Between the Serotonin Transporter and Norepinephrine Transporter Genes in Anorexia Nervosa

“…We also did not observe the increased S allele frequency seen in case-control study AN patients possibly due to clinical and/or genetic heterogeneity, variability of linkage disequilibrium between the 5-HTTLPR and another susceptibility allele in different samples, or population stratification affecting the case-control findings. Supporting population stratification, S allele frequencies in case-control study controls (Di Bella et al, 2000;Sundaramurthy et al, 2000;Fumeron et al, 2001) and in the nontransmitted alleles reported here range from 0.36 to 0.49 (w 2 ¼ 9.48, df ¼ 3, p ¼ 0.024) and S allele frequencies range from 0.11 to 0.70, worldwide (Gelernter et al, 1999). We used the TDT to diminish problems due to population stratification.…”

“…Rare variants include a 15-repeat allele (Nakamura et al, 2000) with undetermined effect on transcription. Case-control studies (Di Bella et al, 2000;Sundaramurthy et al, 2000;Fumeron et al, 2001) demonstrate a trend towards increased frequency of the S allele, and S/S or S/L genotypes in AN patients, reaching statistical significance for AN-BP patients once (Di Bella et al, 2000) (p ¼ 0.020, odds ratio 1.9, 95% CI 1.1À3.1). However, the one family-based study (Hinney et al, 1997), which used the transmission disequilibrium test (TDT) (Spielman et al, 1993) and 55 trios (AN child+ parents), provided no evidence for preferential transmission of the S allele as 52 S/L parents transmitted 27 S and 25 L alleles to AN children (p ¼ 0.90).…”

Association of a functional 5-HT transporter gene polymorphism with anorexia nervosa and food intake

“…[8][9][10] Our result might be a false positive because the AN sample is small. Nevertheless, in the more recent studies, 8,9 an excess of S allele was found in AN although this was not statistically significant. The discrepancy with Hinney et al 10 could be due to a different selection of patients.…”

Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health

“…For example, while some studies show evidence of association between 5-HTTLPR and depressive symptoms, [5][6][7] others do not. [8][9][10][11] An ambiguous pattern of association also exists for ADHD, [12][13][14][15] with few studies reporting association for eating disorders [16][17][18] or conduct disorders. 19,20 The evidence is also conflicting for schizophrenia.…”