Lack of association between variations in the melanocortin 5 receptor gene and bipolar disorder.
OBJECTIVE
The melanocortin 5 receptor gene maps to the bipolar susceptibility locus on chromosome 18p11.2. Given the biological role of melanocortins and their influence on the hypothalamic-pituitary-adrenal axis, the melanocortin 5 receptor gene is a plausible candidate gene for bipolar disorder. We tested the hypothesis that the potential functional variation Phe209Leu confers susceptibility to bipolar disorder in a case-control study.


METHODS
Genotypes for two variations in the coding region and one variation approximately 7 kb upstream from the coding region were obtained from 345 unrelated bipolar I patients and 275 control samples. Genotypes and allele frequencies were compared between groups using chi(2) contingency analysis.


RESULTS
Allele frequencies of the Phe209Leu polymorphism did not differ significantly between bipolar patients and controls (P=0.679). Allele frequencies of the C744T and the intergenic A/G polymorphism did not differ significantly between bipolar patients and controls. All variations were in strong linkage disequilibrium.


CONCLUSIONS
Variations in the melanocortin 5 receptor gene are unlikely to confer susceptibility to bipolar disorder in this sample. Further studies are required to elucidate the susceptibility locus for bipolar disorder on chromosome 18p11.
Lohoff
Falk W
FW
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, 19104-6140, USA. lohoff@mail.med.upenn.edu
Berrettini
Wade H
WH
D001714:Bipolar Disorder / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018043:Receptors, Corticotropin / Q000235:genetics*; D044101:Receptors, Melanocortin; D012016:Reference Values
D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor