Association Studies of Candidate Genes in Bipolar Disorders

Abstract

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

“…In total, 17 population-based studies 9,14,33,34,38,46,50,51,56,60,61,66,[68][69][70] and six family-based studies 12,32,42,53,63,74 were about 5-HTTLPR. A total of 16 population-based studies 27,33,35,38,41,47,[49][50][51]54,56,58,60,61,70,75 and four family-based studies 12,52,57,63 were about the intron 2 VNTR. Among the population-based studies, some used matched controls according to the ethnicity 41,47,50,60,66,69 and others explicitly verified the ethnic homogeneity of the sample through the ancestry history.…”

“…51 The remaining studies mentioned that the sample was ethnically homogeneous. 9,14,34,35,49,54,58,61,68,70,75 5-HTTLPR meta-analysis In total, 17 population-based studies comprised 1712 cases (ie 3424 alleles) and 2583 controls, whereas six family-based studies comprised 587 trios. Summaries are shown in the Tables 1 and 2.…”

“…According to the forest plot of the 5-HTTLPR, Mynett-Johnson et al (2000), 12 Hauser et al (2003) 34 and Rotondo et al (2002) 9 stood apart as an apparent cluster. The forest plot of the intron 2 VNTR showed Kunugi et al, 38 Heiden et al (2000) 35 and Collier et al (1996b) 58 as an apparent cluster. However, we could not identify any particular characteristics shared by these studies that might cause them to stand apart.…”

Investigação de genes candidatos para psicoses funcionais: estudo caso-controle com mães e crianças (população de alto risco)

“…Apenas um estudo encontrou associação do alelo DRD3 Ser e a suscetibilidade de transtorno bipolar (Parsian A. et al, 1995), outros estudos não confirmaram esta associação (Heiden et al 2000, Chiaroni P. et al, 2000.…”

“…Estudos posteriores são ainda inconclusivos, pois muitas pesquisas não detectaram a mesma associação (Heiden et al, 2000, Kirov et al, 1999Waldman et al, 1998. Georgieva et al (2002) analisaram trios e comparou esquizofrenia, transtorno bipolar e esquizoafetivo e não encontrou nenhuma distribuição preferencial de alelos nestes grupos, porém a presença do alelo 10 foi associado com gravidade e maior freqüência de alucinações, embora, estes resultados não tenham sido significantes em teste de análise múltipla.…”