Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca2+ -activated K+ channel to genetic predisposition to anorexia nervosa

• Published in: Journal of psychiatric research Vol. 41; no. 1; pp. 160 - 167
• Main Authors: Koronyo-Hamaoui, Maya, Frisch, Amos, Stein, Daniel, Denziger, Yardena, Leor, Shani, Michaelovsky, Elena, Laufer, Neil, Carel, Cynthia, Fennig, Silvana, Mimouni, Mark, Ram, Anca, Zubery, Eynat, Jeczmien, Pablo, Apter, Alan, Weizman, Abraham, Gak, Eva
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.01.2007
• Subjects: Adult and adolescent clinical studies; Anorexia nervosa; Biological and medical sciences; Eating behavior disorders; Medical sciences; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; N-Methyl- d-aspartate glutamate receptor; SK3 (hSKCa3, KCNN3); Transmission disequilibrium test; Haplotype-based relative risk; Anorexia nervosa; NR2B (GRIN2B); Calcium; Extracellular calcium-sensing receptor; Ionic channel; Glutamate receptor; Eating disorder; Genetic determinism; Inorganic element; Risk factor; Predisposition; NMDA; Genetics; NMDA receptor; KCNN3); Haplotype-based relative risk; Transmission disequilibrium test; Haplotype; Potassium; Anorexia nervosa; N-Methyl-D-aspartate glutamate receptor; NR2B (GRIN2B); SK3 (hSKCa3
• DOI: 10.1016/j.jpsychires.2005.07.010
• ISSN: 0022-3956

Abstract Since identification of the genetic component in anorexia nervosa (AN), genes that partake in serotonergic and dopaminergic systems and in hormonal and weight regulation have been suggested as potential candidates for AN susceptibility. We propose another set of candidate genes. Those are genes that are involved in the signaling pathway using NMDA-R and SK channels and have been suggested as possible effectors of NMDA-R driven signaling. The role of NMDA-R in the etiology of schizophrenia has already been substantiated on various levels. Several studies based on population and family groups have implicated SK3 in schizophrenia and more recently in AN as well. Our study group consisted of 90 AN family trios. We examined the transmission of two potentially functional polymorphisms, 5073T>G polymorphism in the gene encoding the NR2B subunit of NMDA-R and CAG repeats in the coding region of SK3 channel gene. Using HHRR and TDT approaches, we found that both polymorphisms were preferentially transmitted to AN offspring (TDT yielded χ2 = 5.01, p = 0.025 for NR2B 5073G alleles and χ2 = 11.75, p < 0.001 for SK3 L alleles including >19 repeats). Distribution analysis of the combined NR2B / SK3 genotypes suggests that the contribution of both polymorphisms to AN risk is independent and cumulative (OR = 2.44 for NR2B GG genotype and OR = 3.01 for SK3 SL and LL genotypes, and OR = 6.8 for the combined NR2B / SK3 genotypes including high-risk alleles). These findings point to the contribution of genes associated with the NMDA-R signaling pathway to predisposition and development of AN.