We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism.
We examined two large families segregating bipolar disorder, for linkage with the genes encoding dopamine beta-hydroxylase, the dopamine transporter DAT1, the dopamine D2, D3 and D5 receptors, and the alpha-1, alpha-5 and beta-1 subunits of the GABAA receptor.
In order to investigate the validity of these results and to estimate how broadly applicable they are, we performed a linkage study between bipolar affective disorder and two DNA markers (D21S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three European centres and Brazil.
Since IMP has been proposed to be the potential target of lithium, a drug commonly used for the treatment of bipolar disorder, we proceeded to characterize the cognate transcript.
Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49.
In order to determine the possible role of the MAO region in susceptibility to affective disorders in an independent sample, we have genotyped 83 probands of bipolar affective disorder families, 56 sets of parents of bipolar probands, and 84 normal controls for intronic simple sequence repeat polymorphisms of the MAO-A and MAO-B genes.
Linkage analyses using 16 DNA markers covering more than 50 cM from chromosome 4pter-4p12, including candidate genes encoding the dopamine D5 receptor and an adrenergic receptor (2C), were performed in two Danish families with bipolar affective disorder.
Future studies are therefore need to determine whether allelic variants of the INPP1 gene are associated with a favourable efficacy of lithium in manic-depressive illness.
Family-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5.
We attempted to test the hypothesis that there was allelic association between polymorphisms around the tyrosine hydroxylase locus and bipolar affective disorder.
While positive associations between TH and bipolar affective disorder have been found in several studies, many studies have failed to reproduce these results.
Two enzymes involved in the phospholipase C signalling system, namely the myo-inositol monophosphatase (IMPase) and the inositol polyphosphate 1-phosphatase (IPPase), have been postulated as targets for the therapeutic action of lithium in manic-depressive illness.
Family-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5.