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Vincenzo De Luca

Publications and source records attributed to Vincenzo De Luca.

At least 19 recordsLinked to original sources
PubMed2007

Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: analysis of suicidality in schizophrenia and bipolar disorder.

The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behavior by a genetic association between the 5-HT2A C102T silent polymorphism and suicidality in patients with major depression. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific expression of the 5-HT2A gene, and find that the ratio of C/T allele expression in the pre-frontal cortex of heterozygous suicide victims (n = 10) was significantly decreased in comparison with the non-suicide group (n = 10) (P = 0.049). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect the inheritance of suicidal behavior. Thus we examined the parental origin of specific alleles for genetic association in a genetic family-based sample of major psychoses in which information on suicidal behavior was available. No association between the 5-HT2A C102T polymorphism and suicidal behavior in major psychoses was detected with the transmission/disequilibrium test (TDT).

Adult↗
PubMed2007

Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia.

Based on the dopaminergic hypothesis, the dopamine D(1) receptor gene (DRD1) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (-800T/C, -48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case-control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi-square in both samples (P-value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the -800T/-48A/1403C and the -800C/-48G/1403T. Considering each group individually, the -800C/-48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P-value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P-value = 0.16) When the estimated haplotype counts of both samples were combined, the global chi(2) was significant (P-value = 0.00085) and the nominal P-value for the haplotype -800C/-48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the -800C/-48G/1403T haplotype may be considered as a risk factor for BP I disorder.

Adult↗
PubMed2006

Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response.

Dopamine D1 receptors (D1) in the prefrontal cortex have been implicated in the modulation of cognitive processes as well as both positive and negative symptoms of schizophrenia. Therefore pharmacologic agents with potent D1 effects such as clozapine may influence the symptoms of schizophrenia (SCZ). Genetic variation in the D1 receptor gene (DRD1) may help to explain some of the variability in patient response to antipsychotics (APs). This study investigates the effect of four single nucleotide polymorphisms (SNPs) in DRD1 on clozapine response in two distinct SCZ populations (Caucasian and African American) refractory or intolerant to conventional APs. This study included 183 Caucasian and 49 African American schizophrenics diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (revised third or fourth edition). Genotyping was determined by 5'-exonuclease fluorescence assays. Within each population genotype, allele, allele +/- and haplotype frequencies were compared against dichotomous and quantitative measures of treatment response. Linkage disequilibrium analysis was also performed. In the Caucasian sample, no associations were observed for individual SNP tests. However, a rare three-marker haplotype predicted poor response. In the African American sample, the rs265976 variant and another three-marker haplotype were associated with cLozapine response. Although we did not find an association between the rs4532 SNP (-48 A/G, recognized by a DdeI restriction cut site) and cLozapine response as reported by Potkin et al. (2003), a trend in the same direction was observed as well. Our findings suggest that the rs4532 SNP may have a small effect if any. Further studies in larger, independent samples are required to validate these findings.

Adult↗
PubMed2006

Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients.

Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication. Abnormalities in dopaminergic activity in the nigrostriatal system have been most often suggested to be involved because the agents which cause TD share in common potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD. The most consistent findings have been found with the Ser9Gly polymorphism of the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for antipsychotics, only a few polymorphisms in DRD2 have been investigated for their potential involvement in the aetiology of TD. In the present study, we investigated 12 polymorphisms spanning the DRD2 gene and their association with TD in our European Caucasian (n=202) and African-American (n=30) samples. Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003; Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2 genotypes were not significantly associated with TD severity as measured by AIMS (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T (p=0.071). Both TD and total AIMS scores were found to be significantly associated with two-marker haplotypes containing C939T and C957T (p=0.021 and p=0.0087 respectively). Preliminary results indicated that C957T was also associated with TD in our African-American sample (p=0.047). Taken together, the present study suggests that DRD2 may be involved in TD in the Caucasian population, although further studies are warranted.

Adult↗
PubMed2006

Expressed sequence tags from Madagascar periwinkle (Catharanthus roseus).

The Madagascar periwinkle (Catharanthus roseus) is well known to produce the chemotherapeutic anticancer agents, vinblastine and vincristine. In spite of its importance, no expressed sequence tag (EST) analysis of this plant has been reported. Two cDNA libraries were generated from RNA isolated from the base part of young leaves and from root tips to select 9,824 random clones for unidirectional sequencing, to yield 3,327 related sequences and 1,696 singletons by cluster analysis. Putative functions of 3,663 clones were assigned, from 5,023 non-redundant ESTs to establish a resource for transcriptome analysis and gene discovery in this medicinal plant.

ATP-Binding Cassette Transporters↗
PubMed2006

Identification of a low vindoline accumulating cultivar of Catharanthus roseus (L.) G. Don by alkaloid and enzymatic profiling.

The Madagascar periwinkle [Catharanthus roseus (L.) G. Don] is a commercially important horticultural flower species and is the only source of the monoterpenoid indole alkaloids (MIAs), vinblastine and vincristine, key pharmaceutical compounds used to combat a number of different cancers. The present study uses high performance liquid chromatography for metabolic profiling of the MIAs extracted from seedlings and young leaves of 50 different flowering cultivars of C. roseus to show that, except for a single low vindoline cultivar (Vinca Mediterranean DP Orchid), they accumulate similar levels of MIAs. Further enzymatic studies with extracts from young leaves and from developing seedlings show that the low vindoline cultivar has a 10-fold lower tabersonine-16-hydroxylase activity than those of C. roseus cv. Little Delicata. It is concluded that rapid metabolic and more selective enzymatic profiling of Catharanthus mutants could be useful for the identification of a range of altered MIA biosynthesis lines.

Alkaloids↗
PubMed2006

Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia.

A large body of evidence suggests that suicidal behavior is associated with altered noradrenergic neurotransmission. Norepinephrine is degraded by monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). Our hypothesis is that the genes encoding MAOA and COMT might contain genetic variants conferring increased risk for suicidal behavior in schizophrenia and that both genes may interact each other. In order to test this hypothesis, we genotyped the promoter VNTR polymorphism in the MAOA gene and three COMT polymorphisms: -287A>G, Val/Met and 3'UTR C Ins/Del in a cohort of 270 schizophrenics in which 92 attempted suicide. No association between suicide attempt and the MAOA VNTR (P = 0.382), Val108/158Met (P = 0.788) or -287A>G (P = 0.420) polymorphisms was found, however, a slight significant finding was found for 3'UTR polymorphism (P = 0.050). Haplotype analysis for COMT gene revealed no association between suicide attempts and haplotype distribution (P = 0.451). As we tested for epistasis between MAOA VNTR and COMT Val/Met, we found no significant interaction in conferring risk for suicide attempts (P = 0.545). These results suggest that epistasis between MAOA and COMT genes may not influence suicidal behavior in patients with schizophrenia.

Adult↗
PubMed2006

Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia.

Cholinergic dysfunction is one of the hypotheses for the cognitive deficits of schizophrenia. Neurocognitive deficits, which are well-described clinical features of schizophrenia, may be remediated by nicotine; therefore investigations of nicotinic receptor subtypes is of considerable clinical interest. We typed polymorphisms in CHRNA4 and CHRNB2 genes controlling the expression of neuronal high-affinity nicotinic receptors in 117 Canadian families having at least one schizophrenic patient. Using a family-based association strategy, we performed allele, haplotype and interaction analysis of these two loci. In the families tested, the two cholinergic genes interact to affect schizophrenia in combination (P=0.010), while neither was sufficient alone to confer susceptibility. Our present study provided the first line of direct evidence suggesting that the CHRNA4 gene combined with CHRNB2 receptor gene may be linked to schizophrenia.

Adult↗
PubMed2006

N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels.

The NR2B protein is a critical structural and functional subunit of the NMDA glutamate receptor. The glutamate neurotransmitter system has been implicated in psychosis and schizophrenia, and so we looked for genetic association and measured gene expression in human DNA and brain samples, respectively, of the GRIN2B gene that codes for the NR2B protein. We tested three genetic polymorphisms: G-200T (5'UTR), A5806C and T5988C (both 3'UTR) in 180 matched schizophrenia case-control pairs, 86 schizophrenia nuclear family trios, and 318 bipolar disorder trios (of which 158 probands had psychotic symptoms). We measured brain GRIN2B mRNA levels in schizophrenia, bipolar disorder and unaffected controls (n = 35 each). We detected genetic association between the G-200T marker and schizophrenia (p = 0.002), between T5988C and bipolar disorder (p = 0.02), and between A5806C and bipolar disorder with psychotic symptoms (p = 0.0038). The T-C-C haplotype was transmitted more frequently with bipolar disorder, but less often with schizophrenia, while the G-C-T haplotype was transmitted more often in schizophrenia. Significant differences were found in overall haplotype frequencies between schizophrenia cases and controls (p = 0.005). GRIN2B expression levels in schizophrenia, bipolar disorder and controls were not significantly different. The genetic findings suggest a role for GRIN2B in schizophrenia and bipolar disorder.

Adult↗
PubMed2006

Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia.

A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Adult↗
PubMed2006

Lack of association between the corticotrophin-releasing hormone receptor 2 gene and panic disorder.

Panic disorder is classified as an anxiety disorder and affects 1-3% of the population. An individual suffering from such a disorder may experience unexpected recurrent panic attacks and fear of future attacks. Twin and family studies have pointed towards a strong heritability of the disorder. Stress response and anxiety are thought to be mediated, at least in part, by the corticotrophin-releasing hormone (CRH), which is known to be a regulator of the hypothalamic-pituitary-adrenal pathway. To search for markers conferring genetic susceptibility to panic disorder, we typed three polymorphisms of the CRHR2 gene - CRHR2(CA), CRHR2(GT), and CRHR2(GAT) - in 466 individuals, 183 of whom had DSM-IV panic disorder. Seventy-five case-controls and 101 triad families plus 13 siblings were examined. Case-control association analyses using chi(2) tests yielded no difference in the distribution of the alleles. Linkage analysis using the Transmission Disequilibrium Test showed no preferential transmission of alleles for any of the three markers. Haplotype analysis indicated that allele 7 of CRHR2 (GAT) and 8 of CRHR2 (GT) are in almost complete linkage disequilibrium (P = 0.000 000 1). Although both neurobiology and chromosomal location point to the CHRH2 receptor gene as a candidate for panic disorder, our study indicates that the CRHR2 polymorphisms examined do not confer susceptibility to panic disorder. Further studies investigating additional polymorphisms in this gene and other components of the CRH signalling system may prove useful.

Base Sequence↗
PubMed2006

Serotonin transporter polymorphisms and persistent, pervasive childhood aggression.

OBJECTIVE: The purpose of this study was to examine the potential association of the serotonin transporter (5-HTT) gene and childhood aggression by testing the 5-HTT variable-number-tandem-repeat and serotonin transporter promoter polymorphism (5-HTTLPR), including the recently discovered Lg allelic variant of 5-HTTLPR. METHOD: Clinically referred children displaying extreme aggression, with a minimum 2-year history, were genotyped for 5-HTTLPR (N=77) and 5-HTT variable-number-tandem-repeat (N=78). Analyses compared genotype frequencies of the aggressive children with healthy comparison subjects. RESULTS: The "low expressing" genotypic variants of the 5-HTTLPR polymorphism (S/S, Lg/S, Lg/Lg) were significantly associated with childhood aggression. CONCLUSIONS: This is the first study to report a significant association between the 5-HTTLPR gene and childhood aggression.

Adolescent↗
PubMed2006

Association study between functional polymorphisms in the cytochrome P450 1A2 and 2D6 genes and polydipsia in schizophrenia.

The underlying pathophysiology of polydipsia in schizophrenia is poorly understood. Several studies, however, have suggested that there might be a genetic predisposition to polydipsia. In the present study, using a case-control sample that is independent from the previous family sample, we examined a possible association between polydipsia and functional polymorphisms in the genes of cytochrome P450 (CYP) 1A2 and 2D6, primarily important enzymes to the pharmacokinetics of antipsychotic drugs. Japanese patients with schizophrenia (63 polydipsics and 78 nonpolydipsics) were genotyped for two functional polymorphisms, the 734C/A polymorphism in the CYP1A2 gene and the 2D6*10 allele of the CYP2D6 gene. Neither of the polymorphisms was found to be associated with polydipsia nor was any evidence found that the two polymorphisms have an additive effect on the liability to polydipsia. Our results suggest that the CYP1A2 and CYP2D6 polymorphisms are not likely to play a major role in the development of polydipsia in schizophrenia, although further studies testing other alleles of CYP1A2 and CYP2D6 using different ethnic populations are warranted.

Aged↗
PubMed2005

Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia.

A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Adolescent↗
PubMed2005

Association study between the novel functional polymorphism of the serotonin transporter gene and suicidal behaviour in schizophrenia.

A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of schizophrenia and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with suicide attempts of 290 Caucasian schizophrenic patients. Among these patients, 92 had a history of suicide attempt. No association with history of suicide attempt was found in the multiallelic 5-HTTLPR (p = 0.305), however we found significant association with the intron 2 VNTR polymorphism (p = 0.018). When we performed a haplotype analysis, we found association between suicide attempt and haplotype distribution (p = 0.031). These findings suggest that the intron 2 VNTR polymorphism in serotonin transporter gene may influence suicidal behaviour in schizophrenia.

Adult↗
PubMed2005

Tryptophan hydroxylase 2 gene expression and promoter polymorphisms in bipolar disorder and schizophrenia.

The tryptophan hydroxylase isoform-2 gene (Tph2) is located on chromosome 12 and is expressed primarily in brain tissue. Although the tryptophan hydroxylase isoform-1 gene (Tph1) has been reported to have a genetic association with bipolar disorder and schizophrenia, the Tph1 isoform is expressed at much lower levels than Tph2 (150-fold less in the mouse brain). We hypothesized that bipolar disorder and schizophrenia are associated with abnormal levels of TPH2 mRNA in the brain. TPH2 and beta-actin mRNA levels in postmortem brain were quantified using real-time PCR. mRNA samples provided by the Stanley Foundation Array Collection were derived from the dorsolateral prefrontal cortex (Brodmann Area 46) of 35 bipolar, 35 schizophrenic, and 35 control subjects. There were significant differences in the mRNA levels among bipolar, schizophrenic, and normal subjects [F(2,102)=3.58; p=0.031]. A greater amount of TPH2 mRNA was found in the bipolar group in comparison with control subjects (Tukey's test: p=0.024). Further investigations of Tph2 are needed to clarify the potential role of this gene in the pathophysiology of bipolar disorder.

Adult↗
PubMed2005

Association study of 12 polymorphisms spanning the dopamine D(2) receptor gene and clozapine treatment response in two treatment refractory/intolerant populations.

RATIONALE: Dopamine D(2) receptor blockade is the major basis for the antipsychotic action of typical antipsychotic drugs (AP) and a necessary but not sufficient basis for the antipsychotic action of atypical APs such as clozapine and other multireceptor antagonists which rely, in part, upon 5-HT(2A) antagonism. Genetic factors affecting the density and/or function of D(2) receptors may therefore affect AP response. OBJECTIVES: This exploratory study investigates the effect of 12 single nucleotide polymorphisms (SNPs) spanning the entire dopamine D(2) gene on clozapine response in two distinct schizophrenic populations (Caucasian and African-American) refractory or intolerant to conventional APs. METHODS: This study included 183 Caucasian and 49 African-American DSM-III-R or DSM-IV schizophrenics. Genotyping was determined by 5'-exonuclease fluorescence assays. Within each population genotype, allele, allele +/-, and haplotype frequencies were compared between responders and non-responders by X (2) tests. Linkage disequilibrium analysis was also performed. RESULTS: In the Caucasian sample, no significant associations were found for individual SNP tests; however, two haplotypes were identified as having significant protective effects on treatment outcome. In the African-American sample, individual SNP tests identified the Taq1A, Taq1B, and rs1125394 markers as being predictive of clozapine response. Haplotype analyses identified four protective haplotypes containing these SNPs. In addition, no association between the -141C Ins/Del site and clozapine response was found in either population. CONCLUSIONS: Interindividual variability in clozapine response among treatment refractory/intolerant patients is still not fully understood and likely involves multiple factors. This exploratory analysis suggests that the D(2) receptor gene may be one such factor.

Adult↗