A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases

• Published in: Neuroscience letters 1999-12, Vol.277 (2), p.123-126
• Main Authors: Furlong, Robert A., Ho, Luk W., Rubinsztein, Judy S., Michael, Albert, Walsh, Cathy, Paykel, Eugene S., Rubinsztein, David C.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; affective disorders; Alleles; Biological and medical sciences; Bipolar affective disorder; Bipolar Disorder - genetics; Bipolar disorders; Codon - genetics; Depressive Disorder - genetics; Female; Genetic Carrier Screening; Genotype; Humans; Male; Medical sciences; Membrane Proteins - genetics; Mood disorders; Mood Disorders - genetics; Polymorphism, Genetic - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Unipolar affective disorder; Wolfram syndrome; Wolfram Syndrome - genetics; Wolframin; wolframin gene
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00865-4

A recent report has shown that Wolfram syndrome carriers (heterozygotes) are 26-fold more likely to require psychiatric hospitalization compared with non-carriers, and that Wolfram syndrome heterozygotes may constitute approximately 25% of individuals hospitalized with depression and suicide attempts. We analyzed a His611Arg polymorphism of the wolframin gene by the polymerase chain reaction (PCR) and HhaI restriction digestion, in 158 bipolar I and 163 unipolar major affective disorder cases, and 316 controls. Statistical analyses of allele or genotype frequencies do not support a major role for wolframin in affective disorder. HhaI restriction digestion and sequencing of PCR products from four affective disorder cases showed a heterozygous Ala559Thr change. The Ala559Thr variant was not detectable in 382 controls tested. Thus, the rare wolframin 559Thr allele deserves consideration as a risk allele for affective disorder.