Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: No association with Schizophrenia

Seeman, Philip; Ulpian, Carla; Chouinard, Guy; Tol, Hubert H.M. Van; Dwosh, Hy; Lieberman, Jeffrey A.; Siminovitch, Katherine A.; Liu, Ivy S.C; Waye, John S.; Voruganti, Puru; Hudson, Craig J.; Serjeant, G. R.; Masibay, Arni S.; Seeman, Mary V.

doi:10.1002/ajmg.1320540419

Cited by 63 publications

(27 citation statements)

References 34 publications

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“…The DRD4 gene shows a high degree of genetic variation in human populations. These include a Ϫ11CϾT, a ϩ31GϾC (11GlyϾArg) (Cichon et al 1995), a 12-base pair (bp) repeat in exon I (Catalano et al 1993), a 13-bp deletion in exon I (Nothen et al 1994), a (G)n mononucleotide repeat polymorphism in intron I (Petronis et al 1994), a ϩ581TϾG (194ValϾGly) (Seeman et al 1994), a 48-bp repeat polymorphism in exon III (Van Tol et al 1992), and polymorphisms in the upstream region of the gene mentioned in this study (Mitsuyasu et al 1999). To date, none of these polymorphisms have shown evidence of a strong genetic association with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

et al. 2001

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The human dopamine D4 receptor (DRD4) is of major interest in molecular studies of schizophrenia and personality traits. We examined the association of schizophrenia and polymorphisms in the upstream region of the DRD4 gene (Ϫ768GϾA in the negative modulator region; Ϫ521CϾT, Ϫ376CϾT, and Ϫ291CϾT in the cell typespecific promoter region; and Ϫ616CϾG between the two regions) in 208 schizophrenic patients and 210 normal controls. No significant difference in genotype and allele frequencies was observed between the two groups, indicating that these polymorphisms do not make a major contribution to the pathogenesis of schizophrenia. We also studied the association of polymorphisms in the upstream region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with personality traits in 173 Japanese individuals who completed the temperament and character inventory (TCI). The Ϫ768GϾA polymorphism was significantly associated with reward dependence (P ϭ 0.044), while no significant association was observed between novelty seeking and polymorphisms in the upstream region or the exon III repeat polymorphism of the DRD4 gene.

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Section: Discussionmentioning

confidence: 99%

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

et al. 2001

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“…Allele frequencies have been reported as 4% for A2 in Italians. A single T-G base pair substitution in exon 3, which codes for the fifth transmembrane region has been characterized, which substitutes glycine for valine at amino acid position 194 (Seeman et al 1994). This polymorphism has only been demonstrated in people of African ancestry with an allele frequency of 0.125, but has not been observed in Caucasians.…”

Section: Additional Polymorphisms Of Drd4mentioning

confidence: 99%

Dopamine D4 Receptor Gene Novelty or Nonsense?

Paterson

Sunohara

Kennedy

1999

Neuropsychopharmacology

154

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“…18 Most of the presently known variations, such as the 48-bp VNTR in the third exon 19 or the 12-bp VNTR in the first exon, 20 affect the size of the receptor, but some SNPs have also been shown. 21,22 However, reports on the effects of these structural variations on the receptor functioning and on the normal and pathological personality traits are controversial. 13,23 Recently, further polymorphic genes have been shown to influence the effect of the long allele of the DRD4 gene on NS, such as the cathecol O-methyltransferase (COMT) gene and the serotonin transporter promoter region.…”

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Association between Novelty Seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene

et al. 2000

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Association between the human personality trait 'Novelty Seeking' and the polymorphism of the DRD4 gene was first reported by Ebstein 1 and Benjamin 2 in 1996. This was soon followed by replication studies in various ethnic groups and by studying the role of other neurotransmitter receptor and transporter genes in the genetic determination of human temperament. More recently, several polymorphic sites of the upstream regulatory region of the DRD4 gene have been described.3 Among these the −521 C/T single nucleotide polymorphism (SNP) was shown to be associated with the Novelty Seeking (NS) scores of the Temperament and Character Inventory (TCI) in a Japanese male population. 4 We have investigated the −521 C/T SNP polymorphism in a Caucasian (Hungarian) population, 5 and here we report a replication of the Japanese findings, in an association study involving 109 healthy Hungarian volunteers. We found a weak association between NS and CC vs CT or TT genotypes (P Ͻ 0.06). Examination of this relation in male and female sex groups, however, strengthened the association for females (P Ͻ 0.01), but showed no genotypic effect for males. Molecular Psychiatry (2001) 6, 35-38. Human temperament, as measured by various selfreport questionnaires including TPQ (or a new version known as TCI) 6 and NEO-PI-R, 7 was shown to have considerable inherited components.8 Novelty Seeking (NS) is one of the four dimensions in the psychobiological model of temperament, which are thought to be independently heritable, and manifested from an early age. 9 The NS scale was designed to measure exploratory, impulsive and extravagant behavior, and has been related to the dopamine system by Cloninger. Searching for association between common genetic polymorphisms and specific personality traits, recent studies have concentrated on distinct candidate genes. First, the variable number of 48-bp repeats (VNTR) in the third exon of the human dopamine D4 receptor gene (DRD4) was shown to be correlated with the personality trait of Novelty Seeking, as measured by the TPQ 1 or the NEO-PI-R, 2 although the replications of the initial findings have been controversial. [10][11][12][13] Further studies concerning the regulatory region of the genes encoding receptors and transporters involved in neurotransmission revealed associations between a novel polymorphism of the DRD4 promoter region and NS in Japanese subjects. 4 This polymorphism is a CϾT substitution in a CpG island at one end of a cell-type specific regulatory element, between −591 and −123 bp relative to the first nucleotide of the DRD4 gene.14 Using a transient expression system, the −521 T allele was shown to be approximately 40% less active than the −521 C variant in a human retinoblastoma cell line, 4,15 suggesting the relevance of this polymorphism to the dopaminergic system. Moreover, a significantly higher frequency of the CC genotype was found among schizophrenic patients. 15Previously we have described the distribution of −521 C and −521 T alleles in a nonclinical Hungarian populati...

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Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: No association with Schizophrenia

Cited by 63 publications

References 34 publications

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

Dopamine D4 Receptor Gene Novelty or Nonsense?

Association between Novelty Seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene

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