title: CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.
abstract: The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.
authors.affiliation: Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Koronyo-Hamaoui
authors.forename: Eva
authors.initials: E
authors.lastname: Gak
authors.forename: Daniel
authors.initials: D
authors.lastname: Stein
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Yardena
authors.initials: Y
authors.lastname: Danziger
authors.forename: Shani
authors.initials: S
authors.lastname: Leor
authors.forename: Elena
authors.initials: E
authors.lastname: Michaelovsky
authors.forename: Neil
authors.initials: N
authors.lastname: Laufer
authors.forename: Cynthia
authors.initials: C
authors.lastname: Carel
authors.forename: Silvana
authors.initials: S
authors.lastname: Fennig
authors.forename: Marc
authors.initials: M
authors.lastname: Mimouni
authors.forename: Alan
authors.initials: A
authors.lastname: Apter
authors.forename: Boleslav
authors.initials: B
authors.lastname: Goldman
authors.forename: Gad
authors.initials: G
authors.lastname: Barkai
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000856:Anorexia Nervosa / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007557:Israel; D007585:Jews; D011110:Polymorphism, Genetic; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics*; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: C406328:KCNN3 protein, human; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels