Genetics variants in the NEGR1 gene, strongly expressed in the brain, have been reported to affect the neuronal control of food intake therefore inducing obesity. With the same rationale, we hypothesized that this genetic variability may be associated with psychological traits commonly displayed by eating disorder (ED) patients and/or with the risk for the disorder. We analyzed 21 tag-single-nucleotide polymorphisms (SNPs) in the coding sequence and adjacent regions of the NEGR1 gene. A total of 169 ED patients (106 with anorexia nervosa (AN) and 63 with bulimia nervosa (BN)) and 312 healthy subjects were genotyped. Personality traits and general psychopathological symptoms were assessed by the Eating Disorders Inventory Test-2 (EDI-2) and Symptom Checklist 90 Revised inventories. None of the SNPs or haplotypes analyzed were associated with a greater risk of ED or correlated with anthropometric parameters. However, in patients with BN, four SNPs (rs12740031, rs10789322, rs6659202 and rs591540) correlated with the scores in Drive for Thinness (DT), Ineffectiveness (I) and Interoceptive Awareness (IA) (Bonferroni-P<0.05 in all instances). The first two SNPs along with rs954299 and rs2422021 formed a haplotype block, which showed a consistent association with the EDI-2 score in BN patients (Bonferroni-P=0.01). A subsequent three-SNP sliding-window approach identified a central area, encompassing both the haplotype block and the individually relevant SNPs that strongly correlated with the scores of BN patients in DT, I, IA and Bulimia. No associations were identified in the AN group. These preliminary results indicate that NEGR1 could be an important locus influencing certain personality dimensions in BN patients.
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We are thankful to the Spanish Genotyping National Centre (CEGEN-ISCIII) in Santiago de Compostela (Spain), headed by Dr Angel Carracedo, for its valuable technical assistance. This work has been supported in part by the Alicia Koplowitz Foundation, Madrid, Spain, and grant GR10022 from Junta de Extremadura, Consejeria de Economia, Comercio e Innovacion, Merida (Spain).
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website
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Gamero-Villarroel, C., González, L., Gordillo, I. et al. Impact of NEGR1 genetic variability on psychological traits of patients with eating disorders. Pharmacogenomics J 15, 278–283 (2015) doi:10.1038/tpj.2014.53
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