Lack of association of DRD3 and CNR1 polymorphisms with premenstrual dysphoric disorders (original) (raw)
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No association of DRD3 and CNR1 polymorphisms between Premenstrual Dysphoric Disorders
Iranian Journal of Reproductive Medicine
Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized with physical and affective symptoms during the luteal phase of susceptible women. The aim of this study was to investigate the association of Dopamine D3 receptor (DRD3) polymorphism, and Cannabinoid receptor Type 1 (CNR1) polymorphism with PMDD. Fifty one participants with documented PMDD according to the DSM IV criteria and 51 healthy controls were included in this cross sectional study. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews. The genotyping of DRD3 receptor and Cannabinoid type 1 receptors were performed using Taqmanfluorogenic assay method. Distribution of DRD3 and CNR1 polymorphism was not different between patients and controls. These findings do not support a major role of DRD3, and CNR1 polymorphisms in contributing to susceptibility to premenstrual dysphoric disorder.
American Journal of Obstetrics and Gynecology, 2006
Objective: The purpose of this study was to investigate whether common polymorphisms of key genes that control the serotonin (5-hydroxytryptamine) pathway are associated with premenstrual dysphoric disorder. Study design: The study sample comprised 53 women with clinically diagnosed premenstrual dysphoric disorder (age range, 27-46 years; mean age, 37.7 years) and 52 healthy control subjects (age range, 22-48 years; mean age, 36.2 years). Eight polymorphisms that encode the 5-hydroxytryptamine transporter (LPR, VNTR-2, and 3 0 UTR G/T), tryptophan hydroxylase 1 (TPH1 G-6526A, G-5806T, and A218C), and monoamine oxidase A (monoamine oxidase A promoter VNTR-1 and exon 8 Fnu 4H1) were genotyped. Genotype and allelic frequencies were analyzed by chi-square test and stepwise logistic regression analysis. Results: There was no significant association between any genotype and clinical category and no significant allelic distribution profiles in either the premenstrual dysphoric disorder group or the control group. Conclusion: These findings do not support a major role for common 5-hydroxytryptamine transporter, TPH1, and monoamine oxidase A polymorphisms in contributing to susceptibility to premenstrual dysphoric disorder. Ó 2006 Mosby, Inc. All rights reserved.
American Journal of Medical Genetics - Neuropsychiatric Genetics, 2006
Background: Studies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE). Aim: To investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE. Methods: PE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 1,022 controls from a population-based sample. In total, we tested associations between PE and 11 single-nucleotide polymorphisms in the dopamine receptor D1, D2, and D3 genes and in the COMT gene. Outcomes: We found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMTlinked loci (rs4680 and rs4818) had significant associations after correction for multiple testing. Results: 1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that causes a valine-to-methionine substitution. The other polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus, indicating that they capture the same effect. Surprisingly, the rs4680 variant that was statistically significantly more prevalent in the PE group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels. Clinical Translation: Drugs targeting the dopaminergic system could affect PE symptoms. Strengths and Limitations: No replication sample was available for the present study; thus, our findings should be interpreted with caution. Moreover, a limitation of our study is the small sample in the context of genetic association studies (although it should be mentioned that genetically informative samples with phenotypic information about PE symptoms are scarce, and most previous genetic association studies of PE have used samples of similar or smaller size). However, our results are plausible: we report an association between one of the most extensively studied and understood genetic polymorphisms in psychiatric research and PE, and our results are in line with the long-standing hypothesis that dopamine influences human ejaculatory function. Conclusions: We report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated. Jern P, Johansson A, Strohmaier J, et al. Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation.
2002
Seasonal affective disorder (SAD) and premenstrual dysphoric disorder (PMDD) share many clinical features, and have been associated with brain serotonin dysfunction. Females with SAD frequently fulfil the diagnostic criteria for PMDD. A polymorphism in the serotonin transporter promoter gene (5-HTTLPR) has been associated with SAD. We investigated the role of family history and 5-HTTLPR in female SAD patients with and without PMDD. Forty-four SAD females with, and 43 SAD females without PMDD, were genotyped for 5-HTTLPR. Family history of affective disorders in first degree relatives was assessed. An association between the presence of PMDD and family history (P50.0029) and 5-HTTLPR long / short allele-heterozygosity (P50.033) was found in females with SAD. PMDD and SAD may share genetic vulnerability factors, one candidate gene being 5-HTTLPR. The elevated rate of affective disorders in relatives of patients with SAD and PMDD suggests higher genetic vulnerability in this subgroup when compared to patients with SAD alone. Steinberg et al., 1999), and m-chloro-0924-977X / 02 / $ -see front matter
Premenstrual dysphoric disorders: a diversified cluster of vulnerability traits to depression
Acta Psychiatrica Scandinavica, 1997
Some biological factors which have been shown to be abnormal in subgroups of women with dysphoric premenstrual syndromes (PMS) have not been limited to the symptomatic late luteal phase of the menstrual cycle, but also existed during the non-symptomatic mid-follicular phase of the cycle. Personality, cognitive functions, a, and imidazoline binding, sensitivity to inducement of panic attacks, relative hypothyroidism, and some but not all serotonergic functions of women with dysphoric PMS differ from those with no PMS, and also differ during a non-symptomatic phase of the cycle. It is suggested that premenstrual symptoms are an expression of vulnerability traits that might surface in response to a trigger. Such traits are probably diverse, and the nature of the symptoms might depend upon the underlying trait. It is postulated that some vulnerability traits to specific premenstrual syndromes might also be vulnerability traits to depression or anxiety in general.
Polymorphisms in the Dopamine D4 and D2 Receptor Genes and Reproductive and Sexual Behaviors
Human reproductive and sexual behaviors are heritable and may represent integral life history traits that are likely partially subserved by the dopamine system. Two dopamine receptor polymorphisms, DRD4 48bp VNTR and DRD2 TaqI A, were examined in relation to the Sexual-Orientation Inventory (SOI), age at first sexual intercourse, desired age of marriage, and desired age to have children in 195 (45% male) individuals from a general student population. As DRD4 7R alleles have been associated with migratory behavior, we also examined whether those with more 7R alleles had a greater frequency of multi-racial ancestries. Minor alleles of both polymorphisms (7R and A1 respectively) are believed to decrease the function of their respective receptors. Individuals with DRD4 7R alleles were more likely to have had sexual intercourse and to desire children earlier in life. In addition, DRD4 7R+ individuals were more likely to report multi-racial ancestries. Individuals with DRD2 A1 alleles were more likely to not want children and not want to marry. These results suggest that polymorphisms in the DRD4 and DRD2 genes are meaningfully associated with variation in reproductive and sexual behaviors. These results are provisionally interpreted as consistent with other findings suggesting that DRD4 7R and
Gender effect on association between DRD2 polymorphism and substance dependence in a Spanish sample
Drug and Alcohol Dependence, 2009
Our aim was to examine a possible association between substance dependence and the TaqIA polymorphism of the D2 dopamine receptor (DRD2), a single nucleotide polymorphism (SNP) located at the 3 UTR region of the DRD2 gene. A case-control design stratified by gender was used to analyze the genotypes of this SNP in a sample of 125 substance-dependent patients according to DSM-IV and 203 blood donors recruited as controls in two general city hospitals in Madrid, Spain. Genomic DNA from peripheral blood samples was amplified through PCR to identify the variants of the SNP in the DRD2 gene. Analyses performed with Chi 2 tests revealed that the A1 allele (A1/A1 and A1/A2 genotypes) of the Taq 1A SNP of the DRD2 gene was significantly associated with substance dependence in males, but not in the whole sample. Male patients had significantly higher rates of the A1-containing genotypes than male controls. The finding of an association between substance dependence and the DRD2 gene TaqIA SNP only in males suggests the existence of gender-specific differences in the genetic underpinnings of substance dependence.
Clinical and functional correlates of a dopamine D3 receptor polymorphism
Human Psychopharmacology: Clinical and Experimental, 1995
This is a review of our research on dopamine receptor D3 (DRD3) gene polymorphism in psychiatric patients, We found that heterozygosity at a diallelic BalI polymorphic site in the first exon of the DRD3 gene was associated with schizophrenia, as did another group (Mant et a/., 1994). However others did not reproduce our findings and raised doubts about a possible role of the DRD3 in schizophrenia. More recently, we found that homozygosity for allele 2 at the same site was associated with lower cortisol and ACTH responses to apomorphine. We had also previously reported lower ACTH and cortisol responses to apomorphine in paranoid schizophrenics compared to controls (Mokrani et a/., in press). This suggests that DRD3 polymorphisms might be associated with functional differences that could secondarily influence the expression of schizophrenia, in spite of the lack of clear association with schizophrenia. More generally, classical association studies may be limited in their power to prove or disprove minor gene effects in schizophrenia b'ecause the disorder is heterogeneous and various genes may have additive effects in different patients. Biological measures that are closer to gene effects may be a better way to test candidate genes than the association with a complex clinical phenotype. KEY WORDS-Dopamine, dopamine D3 receptor, association, apomorphine challenge, schizophrenia.