Functional polymorphism of −141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia

Ohara, Koichi; Nagai, Miho; Tani, Kunihiko; Nakamura, Yuhei; Ino, Atsushi; Ohara, Kenshiro

doi:10.1016/s0165-1781(98)00092-4

Cited by 77 publications

(39 citation statements)

References 35 publications

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“…Furthermore, one Polish [155] and one German [156] studies found that the SS genotype was associated with a significant increase in risk of depression. Japanese studies did not find any significant difference between patients with major depressive disorder and controls [157,158]. Likewise, the frequency of the S allele did not differ between the normal subjects and the depressed patients in a Korean population [159].…”

Section: Major Depressive Disorder and 5-httlpr Polymorphismmentioning

confidence: 78%

Molecular epidemiology of major depressive disorder

Kiyohara

Yoshimasu

2009

Environ Health Prev Med

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Major depressive disorder causes significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, major depressive disorder increases the risk of suicidal ideation, attempted suicide and death by completed suicide. There is evidence that chronic stress can cause major depressive disorder. As for genetic factors, only minor susceptibility genes have been reliably identified. The serotonin system provides a logical source of susceptibility genes for depression, because this system is the target of selective serotonin reuptake-inhibitor drugs that are effective in treating depression. The 5-hydroxytryptamine (serotonin) transporter (5-HTT) has received particular attention because it is involved in the reuptake of serotonin at brain synapses. One common polymorphic variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which affects the promoter of the 5-HTT gene, causes reduced uptake of the neurotransmitter serotonin into the presynaptic cells in the brain. The authors discussed the relationship between genetic polymorphisms and major depressive disorder, with special emphasis on the 5-HTTTLPR polymorphism. As the 5-HTTLPR polymorphism was significantly associated with an increased risk of major depressive disorder, the 5-HTT gene may be a candidate for a major depressive disorder susceptibility gene. As major depressive disorder is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for major depressive disorder. Hopefully, in the future we will be able to screen for major depressive disorder susceptibility by using specific biomarkers.

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Section: Major Depressive Disorder and 5-httlpr Polymorphismmentioning

confidence: 78%

Molecular epidemiology of major depressive disorder

Kiyohara

Yoshimasu

2009

Environ Health Prev Med

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“…Case-control studies replicated the finding of an association between −141 C Ins allele and schizophrenia within the Swedish population (P Ͻ 0.05) 3 and in a different group of Japanese patients and controls (P Ͻ 0.042). 2 An association with schizophrenia was also reported in a population from the UK but with the −141 C Del allele (P = 0.02). 12 However, studies in Chinese, 13 North American, 14 German 15 and British 16 subjects failed to identify an association.…”

mentioning

confidence: 80%

“…[1][2][3] In the context of a multiple gene or multifactorial etiology of disease, evidence for association may be more easily detected in a more homogeneous population due to the less heterogeneous gene pool. This is one possible explanation for the inconsistent findings between the current findings and those in the previous family-based study of the Chinese population.…”

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confidence: 99%

Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population

et al. 2002

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A functional polymorphism in the promoter region of the DRD2 gene has been found to be associated with schizophrenia in Japanese 1,2 and Swedish populations. 3 We attempted to replicate these findings in a genetically homogenous Portuguese population using a familybased study design. Analysis of 78 trios revealed evidence for association between the −141 C Ins allele and schizophrenia using the haplotype relative risk (HRR) method ( 2 = 9.30, P = 0.0023). Further examination of this sample using an alternative family-based association analysis method, the transmission disequilibrium test (TDT), of 33 informative matings from the Portuguese trios provided evidence for an allelic association and linkage disequilibrium between the insertion allele and schizophrenia ( 2 = 8.76, P = 0.0031). These consistent results using two alternative family-based association analysis methods replicate the findings of previous reports, and thus further implicate a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia.

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“…Polymorphisms of the DRD2 (dopamine D2 receptor) gene, [6][7][8] which have been associated with differences in DRD2 density, [9,10] reduced D2 receptor binding [11,12] and dopamine synthesis [13] make DRD2 a good candidate for a significant genetic contribution to PTSD. In addition, a synonymous polymorphism, 957C4T (rs6277) [14][15][16] and a deletion polymorphism, 141del C (rs1799732) [17] in the DRD2 gene have been found to be associated with schizophrenia, which shares some of the characteristics of PTSD and is also believed to result from dysregulation of dopamine. Specifically, this mutation has been shown to affect mRNA stability and protein translation of the receptor [18] and affects striatal dopamine D2 binding in healthy subjects.…”

Section: Introductionmentioning

confidence: 99%

The DRD2 gene 957C>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans

et al. 2009

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Background: Variations in genes related to the dopaminergic pathway have been implicated in neuropsychiatric disorders such as schizophrenia, substance misuse, Alzheimer's disease and Post Traumatic Stress Disorder (PTSD). A single nucleotide polymorphism (SNP) (957C4T) and a deletion polymorphism (-141delC) in the DRD2 gene and a SNP (Taq1A) in a gene directly downstream of DRD2 have all been implicated in dopamine functioning in the brain. Methods: To test the importance of these three polymorphisms in PTSD susceptibility, a genetic screen was performed in 127 war veterans diagnosed with PTSD and 228 control individuals without a history of PTSD. Results: No significant association was found between PTSD and the Taq1A or -141delC polymorphisms. However, a significant association was observed with PTSD and the 957C4T polymorphism. PTSD individuals were more likely to carry the C allele compared to the controls (P 5 0.021). Conclusions: Our findings suggest that the 957C4T polymorphism in the DRD2 gene is one of the genetic factors for susceptibility to PTSD. Depression Anxiety 26: 28-33, 2009.

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Functional polymorphism of −141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia

Cited by 77 publications

References 35 publications

Molecular epidemiology of major depressive disorder

Molecular epidemiology of major depressive disorder

Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population

The DRD2 gene 957C>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans

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