title: Interacting genes in lithium prophylaxis: preliminary results of an exploratory analysis on the role of DGKH and NR1D1 gene polymorphisms in 199 Sardinian bipolar patients.
abstract: Lithium represents the first-choice and most effective drug in the treatment of bipolar disorder (BD). While its mechanism of action is far from being totally understood, a large amount of evidence pointed to a role of second messengers mediated pathways and elements of the circadian system in modulating its mood stabilizing effect. In the present paper, we tested the possible association and interaction effect of the nuclear receptor subfamily 1, group D, member 1 (NR1D1) gene and the Diacylglycerol kinase eta (DGKH) gene with the therapeutic response to lithium prophylaxis. Single nucleotide polymorphisms (SNPs) rs12941497 and rs939347 at NR1D1 gene and SNPs rs9315885, rs1012053 and rs1170191 at DGKH gene were genotyped in a sample of 199 Sardinian BD patients characterized for the response to lithium therapy. Genotype and allele frequency distributions did not differ significantly between groups of patients Full Responders and partial/not responders to lithium prophylaxis. Moreover, no significant differences were identified between groups of patients when divided considering the improvement in symptoms after lithium treatment. The interaction analysis did not show a significant effect on these outcomes. While negative, our findings do not exclude an involvement of DGKH and NR1D1 in lithium prophylaxis. Moreover, the lack of statistic interaction might not necessarily correspond to a lack of biologic interaction between the genes studied.
authors.affiliation: Laboratory of Molecular Genetics, Department of Neurosciences B.B. Brodie, University of Cagliari, SS 554, km. 4,500, 09042 Monserrato, Cagliari, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics / Q000517:prevention & control*; D019852:Diacylglycerol Kinase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms
chemical_list: D018020:Lithium Compounds; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D020033:Protein Isoforms; D019852:Diacylglycerol Kinase