Serotonin Transporter Gene and Risk for Bipolar Affective Disorder: An Association Study in a Spanish Population

Gutiérrez, Blanca; Arranz, Maria; Collier, David; Vallès, Vicenç; Guillamat, Roser; Bertranpetit, Jaume; Murray, Robin M.; Fañanás, Lourdes

doi:10.1016/s0006-3223(97)00540-4

Cited by 86 publications

(51 citation statements)

References 15 publications

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“…The ob- served frequencies of the comt alleles in this control sample were: high activity allele ϭ 0.58, and low activity allele ϭ 0.42, and they did not differ between males (0.57͞0.43) and females (0.58͞0.42). The observed frequencies are in very close agreement with frequencies previously reported for another North American caucasian control sample that had also been evaluated psychiatrically (28), as well as for a European sample of Spanish origin, where psychiatric illness had also been excluded (29). Another caucasian control sample of British origin that was not psychiatrically evaluated has been recently described (30) with a higher frequency of the low activity allele in both males and females (0.53).…”

Section: Discussionsupporting

confidence: 89%

“…This report extends our initial findings in this region by providing evidence that activity variation in one of the resident genes can explain aspects of the psychiatric phenotype associated with this genetic interval. It is of interest that previous studies on the comt allele distribution (22,30,42) failed to reveal a major effect of this gene on schizophrenia or bipolar disorder (29), suggesting diagnostic specificity of our finding and a complex contribution of the 22q11 region in the development of the psychiatric phenotype. …”

Section: Discussionmentioning

confidence: 65%

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Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Karayiorgou

Altemus

Galke

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

288

182

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In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3-to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 65%

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Karayiorgou

Altemus

Galke

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

288

182

View full text Add to dashboard Cite

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“…Association was observed between the 5-HTT LPR polymorphism and schizophrenia, with a slightly higher frequency of the allele 528 bp observed in patients. These frequencies differ slightly from those observed in other Spanish populations [Gutierrez et al, 1998] and may be caused by heterogeneity or chance finding. A marginal association was also observed with the 5-HTT VNTR polymorphism: an excess of the 12 repeat allele was observed in patients in comparison with controls (P = 0.05).…”

Section: Discussioncontrasting

confidence: 81%

Serotonergic polymorphisms and psychotic disorders in populations from North Spain

Mata¹,

Arranz²,

Patiño

et al. 2003

American J of Med Genetics Pt B

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There is strong biological evidence relating alterations in the serotonergic system with mental disorders. These alterations may be originated at the DNA level by sequence mutations that alter the functioning of serotonin receptors and transporter. To test this hypothesis we investigated three genetic variants of the 5-HT2A receptor (-1438G/A, 102T/C and His452Tyr) and two variants of the serotonin transporter (a VNTR in the second intron and a 44 bp insertion/delition in the promoter region of the gene) in a clinical sample recruited in a human isolate and in surrounding areas in Northern Spain (N = 257) and in ethnically matched controls (N = 334). No clear association was found between 5-HT2A variants and psychosis. However, marginal associations were observed between the 5-HTT LPR and VNTR variants and psychosis (P≤0.05) indicating a minor contribution to psychosis of genetic alterations in this gene.

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“…48,59 The 31 papers finally selected reported 43 studies related to the review objective in total since each paper frequently reported several separate studies. 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.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2005

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The serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using metaanalytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies-both population-based and family-based studies-investigating the association between BPD and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats (VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03-1.21) for the 5-HTTLPR and 1.12 (95% CI 1.02-1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type (population-based vs family-based; P ¼ 0.41 for the 5-HTTLPR and P ¼ 0.91 for the intron 2 VNTR) nor the sample ethnicity (Caucasian vs non-Caucasian; P ¼ 0.35 for the 5-HTTLPR and P ¼ 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT. Keywords: bipolar disorder; serotonin transporter; polymorphisms; genetics; association study; meta-analysis Bipolar disorder (BPD), also known as manic-depressive illness, is a frequent and severe psychiatric disorder with the lifetime prevalence between 1 and 2% in the general population, being equally distributed across sexes. 1 The etiology is unknown although the presence of a complex dysfunction at multiple levels such as neurotransmitter system, prefrontallimbic-subcortical circuit and neuroendocrinological system has been suggested. 2 Family studies have indicated a marked increase in lifetime risk of the illness in first-degree relatives of the proband, varying between five and 10 times that of the general population. 3 Twin studies have shown an increased risk in monozygotic co-twins compared with dizygotic co-twins of a proband with BPD. The risk in monozygotic co-twins has been estimated at 45-75 times that of the general population. 3,4 Adoption studies have also shown that the risk of BPD is greater in biological relatives than in adoptive relatives of the probands. 5 Most of the segregation studies have shown that the inheritance of BPD cannot be explained b...

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Serotonin Transporter Gene and Risk for Bipolar Affective Disorder: An Association Study in a Spanish Population

Cited by 86 publications

References 15 publications

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Serotonergic polymorphisms and psychotic disorders in populations from North Spain

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

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