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Biomedical subjects

E G Jönsson

Publications and source records attributed to E G Jönsson.

At least 19 recordsLinked to original sources
PubMed2003

Transcription factor AP-2beta genotype, striatal dopamine D2 receptor density and cerebrospinal fluid monoamine metabolite concentrations in humans.

Transcription factor AP-2beta has been suggested to influence brain monoaminergic systems by regulating target genes. In order to explore a possible functional role, AP-2beta genotype was analysed in relation to striatal dopamine D2 receptor density determined in vivo by positron emission tomography in human subjects (n = 52). The AP-2beta genotype was also analysed in relation to cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) in healthy human subjects (n = 90). There was no association between the AP-2beta genotype and measures of dopamine receptor density, or CSF 5-HIAA concentrations. However, AP-2beta genotype was associated with CSF-levels of HVA (in women) and MHPG. These data may suggest a functional involvement of AP-2beta in the dopaminergic system, but should be interpreted with caution until replicated.

Adult↗
PubMed2001

No association between a promoter dopamine D(4) receptor gene variant and schizophrenia.

The dopamine D(4) receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (-521C/T) in the dopamine D(4) receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n = 132) and control subjects (n = 388) were analyzed with respect to the DRD4 - 521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden.

Adult↗
PubMed2001

Identification of four novel polymorphisms in the calcitonin/alpha-CGRP (CALCA) gene and an investigation of their possible associations with Parkinson disease, schizophrenia, and manic depression.

We identified novel polymorphisms in the calcitonin/CGRPalpha (CALCA) gene by direct sequencing of genomic DNA and subsequent genotyping by RFLP (restriction fragment length polymorphism) detection and investigated association with neurological or psychiatric disease. Four novel polymorphic alleles were found: two (g.979G>A and g.4218T>C) represented single nucleotide polymorphisms (SNPs), one consisted of two coupled SNPs in close vicinity to each other (g.1210T>C and g.1214C>G), and one was an intronic 16-bp microdeletion (2919-2934del16). One of the SNPs (g.4218T>C) causes a non-synonymous amino acid change (Leu66Pro) in the third exon, an exon common to both procalcitonin and pro-alpha-CGRP. In a subsequent association study, frequencies of the identified polymorphisms in Parkinson and schizophrenia patients were compared with frequencies in the normal population. No statistically significant association was found in our material. The 16-bp microdeletion polymorphism was present in a family with multiple cases of unipolar or bipolar depressive disorder. Using this polymorphism as marker, cosegregation with the phenotype was observed in the majority of individuals.

Amino Acid Sequence↗
PubMed2001

No association between serotonin 2A receptor gene variants and personality traits.

Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.

Adult↗
PubMed2001

Androgen receptor trinucleotide repeat polymorphism and personality traits.

Human family and twin studies have established considerable heritable components influencing individual differences in personality traits as assessed by self-report questionnaires. We have investigated a trinucleotide repeat polymorphism in the androgen receptor gene and personality traits. Healthy Swedish subjects (n = 335) were assessed with the Karolinska Scales of Personality inventory. There were tendencies (P > or = 0.006) in some scales indicating possible relationships between the androgen receptor allele length and personality traits related to dominance and aggression. However, after correction for multiple testing, no significant differences were found. We conclude that no significant association could be found between the androgen receptor polymorphism investigated and any personality trait, although the tendencies found are worthwhile subjects for replication attempts.

Adult↗
PubMed2000

NURR1 mutations in cases of schizophrenia and manic-depressive disorder.

Transgenic mice lacking the nuclear orphan transcription factor Nur-related receptor 1 (Nurr1) fail to develop mesencephalic dopamine neurons. There is a highly homologous NURR1 gene in humans (formerly known as NOT) which therefore constitutes a good candidate gene for neurologic and psychiatric disorders with an involvement of the dopamine neuron system, such as Parkinson's disease, schizophrenia, and manic-depression. By direct sequencing of genomic DNA, we found two different missense mutations in the third exon of NURR1 in two schizophrenic patients and another missense mutation in the same exon in an individual with manic-depressive disorder. All three mutations caused a similar reduction of in vitro transcriptional activity of NURR1 dimers of about 30-40%. Neither of these amino acid changes, nor any sequence changes whatsoever, were found in patients with Parkinson's disease or control DNA material of normal populations. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:808-813, 2000.

Alleles↗
PubMed2000

Search for the influence of the tyrosine hydroxylase (TCAT)(n) repeat polymorphism on personality traits.

A putatively functional tetranucleotide repeat polymorphism in the tyrosine hydroxylase gene (TH) has been investigated with regard to different aspects of psychopathology. We investigated whether reported associations of this TH polymorphism may reflect associations with common personality traits. Personality was assessed by the NEO Personality Inventory-Revised version (NEO PI-R), in 205 healthy Caucasian volunteers. Tendencies for higher scores in the neuroticism (N) facets, Angry hostility (P=0.008) and Vulnerability (P=0.021), were observed among carriers of one of the alleles (T8). Healthy women with the T6/T10 genotype had significantly higher scores (P=0.001) in the Deliberation and Dutifulness facets (P=0.031) (the Conscientiousness dimension, C) and lower scores (P=0.031) in the Feelings facet (the Openness dimension, O). We concluded that: (1) higher mean scores in the Neuroticism facets among T8 allele carriers are consistent with previous data and warrants further research; (2) the T6/T10 genotype may influence personality among women; (3) these data should be cautiously interpreted in the absence of corroborating data.

Adult↗
PubMed2000

Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.

Adult↗
PubMed2000

Search for association between suicide attempt and serotonergic polymorphisms.

Serotonergic neurotransmission has been implicated in suicidal behavior. Polymorphisms in the genes coding for tryptophan hydroxylase, serotonin receptor 2A and serotonin transporter were investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No significant differences were found for any of the investigated polymorphisms. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar disorder (n = 45), adjustment disorder (n = 37), substance use disorder (n = 37) and personality disorder, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphisms do not represent a major determinant in suicide attempt. However, a highly significant (P = 0.001; odds ratio, 1.47; 99% confidence interval, 1.42-1.53) allelic association between tryptophan hydroxylase and suicide attempt is indicated after pooling our data with literature data. In light of previous data, a possible association between the tryptophan hydroxylase polymorphism and a phenotype that may become differently stratified within differently selected samples of suicide attempters is discussed.

Adjustment Disorders↗
PubMed1999

Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia.

Genetic factors and dopamine receptor dysfunction have been implicated in the pathophysiology of schizophrenia. Recently, an association between a putative functional promoter polymorphism (-141C Ins/Del) in the dopamine D2 receptor gene and schizophrenia was reported. We investigated unrelated Swedish schizophrenic patients (n = 129) and control subjects (n = 179) for the same polymorphism. Similarly to a previous Japanese report, the - 141C Del allele frequency was significantly lower in patients than controls (chi2=4.4, 1 df, p<0.05; odds ratio 0.49, 95% confidence interval 0.26-0.91). The present and previous results may indicate that the -141C Ins/Del dopamine D2 receptor gene polymorphism affects susceptibility to schizophrenia.

Adult↗
PubMed1999

Trend for an association between schizophrenia and D3S1310, a marker in proximity to the dopamine D3 receptor gene.

There is considerable controversy regarding a putative association between schizophrenia and a biallelic BalI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3), although meta-analyses of published data suggest an association. If such an association exists, it may be detectable at markers physically close to DRD3. Accordingly, we conducted a case-control association study using D3S1310, a short tandem repeat polymorphism located approximately 700 kb telomeric to DRD3 on chromosome 3q13.3. The subjects were Swedish patients with schizophrenia (DSM III-R criteria, n = 110) and screened adult controls (n = 83). A trend for a negative association with the 141 bp allele was detected (chi2 = 7.6, d.f. = 1, P = 0.006; odds ratio 0.46, 95% confidence intervals 0.26, 0.81). However, following corrections for multiple comparisons using subgroups (n = 15) the difference was not significant. Also, due to the risk for population stratification in case-control association studies the results must be treated as tentative. If replicated the results may lend further support for the proposition of an association between schizophrenia and DRD3 or a gene in close proximity to DRD3 on chromosome 3q.

Adult↗
PubMed1999

No association between serotonin transporter gene polymorphisms and personality traits.

Human family and twin studies have established considerable heritable components in personality traits as assessed by self-report questionnaires. Recently, an association between a functional polymorphism in the upstream regulatory region of the serotonin transporter gene and neuroticism-related personality traits was reported. Two different serotonin transporter polymorphisms including the previously associated variant were genotyped in two samples of healthy Swedish subjects (n = 127 and n = 178, respectively) assessed with the Karolinska Scales of Personality (KSP) inventory. No statistically significant association between serotonin transporter polymorphisms and any of the eight neuroticism-related KSP scales was found. Thus, the previously reported association between serotonin transporter alleles and neuroticism-related personality traits could not be replicated in the present study.

Adult↗
PubMed1999

Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers.

The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [11C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (-141C Del) and high striatal dopamine receptor density (t= 2.32, P= 0.02). In agreement with some previous studies the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t=2.58, P=0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t= 2.58, P= 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size.

Adult↗
PubMed1999

Lack of association between suicide attempt and a polymorphism at the dopamine receptor D4 locus.

Dopaminergic neurotransmission has been implicated in suicidal behaviour. The 48 bp-repeat polymorphism in the gene coding for dopamine receptor D4 was investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No association between suicide attempts and this polymorphism was observed. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar (n = 45), anxiety (n = 23), adjustment (n = 37) and personality disorders, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphism do not have a major impact on suicidal behaviour.

Adjustment Disorders↗
PubMed1998

Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers.

Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.

Adult↗
PubMed1998

Lack of association between schizophrenia and HLA DQB1 alleles in a Swedish sample.

Three studies have reported a negative genetic association between schizophrenia and HLA DQB1*0602, an allele of the human leucocyte antigen (HLA) DQB1*06 gene. In a sample of ethnic all homogeneous Caucasians living in Sweden, the frequency of HLA DQB1 alleles in patients with schizophrenia (n = 124) was compared with that in a control group (n = 85). No significant differences were found. Together with previous investigations, the present study indicates that the reported genetic association of DQB1*0602 with schizophrenia may be limited to non-Caucasians.

Adult↗
PubMed1998

Failure to replicate an association between a rare allele of a tyrosine hydroxylase gene microsatellite and schizophrenia.

An association between schizophrenia and a rare perfect ten-repeat allele, K1p, of a tetranucleotide microsatellite polymorphism in the tyrosine hydroxylase gene has recently been reported. The rare allele was found only in schizophrenic patients. During treatment with antipsychotic drugs patients with the rare allele displayed lower plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels than those without. We examined Swedish schizophrenic patients (n = 117) and healthy control subjects (n = 76) for the same polymorphism. In contrast to the previous studies, the K1p frequency in patients (4 of 117) tended to be lower than among controls (9 of 76). With all six alleles (K1p, K1i, K2-5) considered there was a significant difference between schizophrenic patients and control subjects. There was no significant difference in HVA and MHPG levels in cerebrospinal fluid from a subset (n = 64) of control subjects with and without the rare allele. The discrepant results warrant further investigation of the tyrosine hydroxylase gene.

Alleles↗