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

Fumeron, Frédéric; Betoulle, D; Aubert, Roberte; Herbeth, Bernard; Siest, Gérard; Rigaud, Daniel

doi:10.1038/sj.mp.4000824

Cited by 68 publications

(48 citation statements)

References 12 publications

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“…As far as we know, four studies have examined the association between 5-HTTLPR and ED. Fumeron et al reported a higher frequency of the S/S genotype of 5-HTTLPR in AN subjects than in normal-weight controls [17], but reports of evidence against these findings [18][19][20] make the association controversial.…”

Section: Discussionmentioning

confidence: 99%

“…The transcriptional activity of the long form allele was more than twice as high as that of the short form allele [16]. As far as we know, four studies have examined the association between 5-HTTLPR and eating disorders (ED) [17][18][19][20]. The insulin receptor is part of a transmembrane tyrosine kinase-mediating intracellular signaling process that leads to the biological actions of insulin [21].…”

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confidence: 99%

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LEPR, ADBR3, IRS-1 and 5-HTT Genes Polymorphisms do not Associate with Obesity

et al. 2007

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Abstract. Obesity is a growing problem and is associated with numerous medical conditions. In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms have been reported which possibly modify human obesity risk. The aim of this study was to determine the incidence of the following polymorphisms in the following genes in 262 obese (BMI≥30) and 138 control (BMI≤25) subjects: leptin receptor (LEPR)-Gln223Arg, B 3 -adrenergic receptor (B 3 -AR)-Trp64Arg, serotonin transporter (5-HTT)-a 44-base pair insertion/ deletion functional polymorphism in the 5-HTTLPR and insulin receptor substrate-1 (IRS-1)-Gly972Arg. Our hypothesis was that these polymorphisms would occur more frequently in the obese population. The polymorphisms were determined by polymerase chain reaction (PCR) and restriction genotyping in study population. In our results, no strong associations were observed between BMI status and these polymorphisms. Weak, though significant, association coefficients obtained with HTT and LEPR loci indicate that the genotype numbers at these loci may depend on BMI status to some extent.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

LEPR, ADBR3, IRS-1 and 5-HTT Genes Polymorphisms do not Associate with Obesity

et al. 2007

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Urwin

Bennetts

Wilcken

et al. 2003

Neuropsychopharmacol

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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 w 2 ¼ 0.01, df ¼ 1, p ¼ 0.921, odds ratio 1.0, 95% CI 0.7À1.5). 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) (w 2 ¼ 0.48, df ¼ 1, p ¼ 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.

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“…Thereafter, numerous studies have shown an association of the S allele with a variety of emotional disorders and psychopathological traits such as the following: suicidality (Anguelova et al, 2003), depression (Caspi et al, 2003), bipolar affective disorder (Bellivier et al, 2002), anxiety disorders (Xu et al, 2006), post-traumatic stress disorder (Lee et al, 2005), eating disorders (Fumeron et al, 2001), impulsivity-aggression (Verona et al, 2006), as well as certain types of alcoholism (Thompson et al, 2000). Healthy individuals homozygous for the S allele exhibit higher levels of depressivity (Gonda et al, 2005) and are more likely to have first-degree relatives with a history of depression (Joiner et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Psychological vulnerability differences in students—Carriers or not of the serotonin transporter promoter allele S: Effect of adverse experiences

Veletza

Samakouri

Emmanouil

et al. 2008

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Aim: To study the effect of the serotonin transporting gene L/S polymorphism on several psychological characteristics in a group of Greek University students. Methods: One hundred eighty-one students were genotyped and classified into two groups: carriers or noncarriers of an S allele. Students were evaluated with a battery of psychological tests (Zung depression rating scale, symptoms check-list-90-R, Eysenck personality inventory); they also answered questionnaires regarding serious past adverse experiences as well as nicotine and alcohol use. Multivariate analysis of variance (MANOVA) was used to check the main effect of genotype and its interaction with both adverse life experiences and scores of psychological tests. Results: No significant differences were detected between the two groups of students regarding scores of the psychological tests. Yet, analysis with MANOVA indicated an interaction between genotype and adversities (k 5 0.838, F 17,158 5 1.802, P 5 0.032). Students who both carry at least one S allele and have faced serious past adverse life experiences have scored higher than carriers of the S allele who have not faced adversities on the following: global severity index (F 1174 5 5.973, P 5 0.016), positive symptoms distress index (F 1174 5 4.518, P 5 0.035), somatization (F 1174 5 4.074, P 5 0.045), depression (F 1174 5 4.971, P 5 0.027), anxiety (F 1174 5 8.112, P 5 0.005), phobic anxiety (F 1174 5 16.421, P < 0.000), and paranoid ideation (F 1174 5 5.143, P 5 0.025). Among students without adversities, those with the LL genotype have scored higher than S allele carriers on the following: depression (t 5 2.680, df 5 75, P 5 0.009), anxiety (t 5 2.629, df 5 75, P 5 0.010), phobic anxiety (t 5 3.350, df 5 75, P 5 0.001), and paranoid ideation (t 5 2.668, df 5 75, P 5 0.009). Conclusion: The S and L alleles seem to interact differently with serious past life adversities in influencing psychological vulnerability. Adversities seem to have a stronger effect on S carriers. LL genotype might be related to the expression of certain more endogenous psychopathological tendencies.

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

Cited by 68 publications

References 12 publications

LEPR, ADBR3, IRS-1 and 5-HTT Genes Polymorphisms do not Associate with Obesity

LEPR, ADBR3, IRS-1 and 5-HTT Genes Polymorphisms do not Associate with Obesity

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

Psychological vulnerability differences in students—Carriers or not of the serotonin transporter promoter allele S: Effect of adverse experiences

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