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

A recent report has shown that Wolfram syndrome carriers (heterozygotes) ar e 26-fold more likely to require psychiatric hospitalization compared with non-carriers, and that Wolfram syndrome heterozygotes may constitute approx imately 25% of individuals hospitalized with depression and suicide attempt s. We analyzed a His611Arg polymorphism of the wolframin gene by the polyme rase chain reaction (PCR) and HhaI restriction digestion, in 158 bipolar I and 163 unipolar major affective disorder castes, and 316 controls. Statist ical analyses of allele or genotype frequencies do not support a major role for wolframin in affective disorder. HhaI restriction digestion and sequen cing of PCR products from four affective disorder cases showed a heterozygo us Ala559Thr change. The Ala559Thr variant was not detectable in 382 contro ls tested. Thus, the rare wolframin 559Thr allele deserves consideration as a risk allele for affective disorder. (C) 1999 Elsevier Science Ireland Lt d. All rights reserved.