Investigation of transcription factor AP-2beta genotype in women with premenstrual dysphoric disorder

doi:10.1016/j.neulet.2004.11.068

Neuroscience Letters

Volume 377, Issue 1, 22 March 2005, Pages 49-52

https://doi.org/10.1016/j.neulet.2004.11.068 Get rights and content

Abstract

It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2β in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2β in regulatory regions, suggesting an involvement of AP-2β in these systems. The gene encoding AP-2β is located on chromosome 6p12–p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2β genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2β correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2β genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2β genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2β genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2β genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.

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Acknowledgements

This study was supported by grants from the Swedish Brain Research Foundation and the Swedish Medical Research Council (#4145). The authors would like to thank Sigrid Sandberg for excellent technical help and Staffan Nilsson for power calculations.

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Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls
2010, Journal of Psychiatric Research
Citation Excerpt :
Estimates of heritability for premenstrual symptoms range from 22% to 37% and are as high as 43.3% for severe premenstrual symptoms (Kendler et al., 1992). Several genetic polymorphisms have been tested for possible association with PMDD (Damberg et al., 2005; Melke et al., 2003) including the following: three variants in the serotonin transporter (SLC6A4), specifically the serotonin transporter gene-linked polymorphic region (5-HTTLPR) (Heils et al., 1995), an intron 2 variable number of tandem repeats (VNTR) (Ogilvie et al., 1996), and a G to T single nucleotide polymorphism (SNP) in the 3′ untranslated region (UTR) (Battersby et al., 1999); an intron 2 VNTR in the gene for transcription factor activating protein 2beta (AP-2beta) (Damberg et al., 2005); gene-based haplotypic variants in genes for estrogen receptor alpha (ESR-1), estrogen receptor beta, and progesterone receptor (Huo et al., 2007). We have previously reported a significant association between PMDD and ESR-1 (Huo et al., 2007); significant associations have also been reported for serotonin receptor 1A (Dhingra et al., 2007) and 5-HTTLPR (Praschak-Rieder et al., 2002).
Premenstrual Dysphoric Disorder (PMDD) is a mood disorder affecting about 5% of women and is associated with substantial morbidity. Albeit inconsistently, PMDD is described as being characterized by heritable personality traits. Although PMDD is a heritable disorder, it is unclear whether any of the heritable susceptibility to PMDD resides in heritable personality traits. In groups of carefully characterized women with PMDD (n = 68) and controls (n = 56), we attempted to determine whether diagnosis-related traits could be confirmed, as well as to determine whether such traits were associated with SNPs in estrogen receptor alpha (ESR-1) that we previously demonstrated were associated with PMDD. We observed 7/25 traits to be significantly different in patients and controls and further showed that 11/12 significant associations observed between these 7 traits and 16 ESR-1 SNPs involved the intron 4 SNPs previously shown to be the locus of the association with PMDD. While several interactions between genotype and diagnosis were observed, the effect of genotype in most instances was in the same direction in patients and controls. These data demonstrate affective state-independent personality traits that distinguish patients with PMDD from controls and further support the relevance of ESR-1 polymorphic variants in the regulation of non-reproductive behaviors.
Hormonal Regulation of the Menstrual Cycle, Mechanisms of Ovulation, Premenstrual Syndromes
2010, Endocrinology: Adult and Pediatric, Sixth Edition
Understanding and Treating Premenstrual Dysphoric Disorder: An Update for the Women's Health Practitioner
2009, Obstetrics and Gynecology Clinics of North America
Citation Excerpt :
Several studies have attempted to delineate the genetic basis for differences in serotonin function and metabolism in women with PMDD. Research into AP-2, 5HT transporter, tryptophan hydroxylase, and monoamine oxidase genotypes has mostly been inconclusive.52,59,60 However, Praschak-Rieder and colleagues61 found an association between PMDD and 5HTLLPR heterozygosity in women with seasonal affective disorder, and Steiner and colleagues46 identified a relationship between polymorphism in the serotonin transporter gene and severity of PMDD symptoms.
Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene
2007, Biological Psychiatry
Premenstrual dysphoric disorder (PMDD) is a heritable mood disorder that is triggered by gonadal steroids during the luteal phase in susceptible women.
We performed haplotype analyses of estrogen receptors alpha and beta (ESR1 and ESR2) in 91 women with prospectively confirmed PMDD and 56 control subjects to investigate possible sources of the genetic susceptibility to affective dysregulation induced by normal levels of gonadal steroids. We also examined associations with the valine (Val)158methionine (Met) single nucleotide polymorphism (SNP) of the gene for catechol-O-methyltransferase (COMT), an enzyme involved in estrogen metabolism and prefrontal cortical activation.
Four SNPs in intron 4 of ESR1 showed significantly different genotype and allele distributions between patients and control subjects. Significant case-control differences were seen in sliding-window analyses of two-, three-, and four-marker haplotypes but only in those haplotypes containing SNPs in intron 4 that were positive in the single-locus analysis. No significant associations were observed with ESR2 or with the COMT Val158Met polymorphism, although the significant associations with ESR1 were observed only in those with the Val/Val genotype.
These are the first positive (albeit preliminary) genetic findings in this reproductive endocrine-related mood disorder and involve the receptor for a hormone that is pathogenically relevant.
Premenstrual dysphoric disorder: Burden of illness and treatment update
2008, Journal of Psychiatry and Neuroscience
Citation Excerpt :
This significant study may identify a source of abnormal estrogen signalling during the luteal phase that leads to premenstrual affective, cognitive and somatic symptoms.20 Previous studies had failed to identify gene polymorphism differences between women with PMDD and control subjects in regard to the serotonin transporter,21,22 the transcription factor activating protein 2,23 tryptophan hydroxylase and monoamine oxidase A promoter22 genes. Overlap of PMDD with genetic liability for MDD, seasonal affective disorder and personality characteristics has been suggested.24,25
Five percent of menstruating women have severe premenstrual symptoms and impairment of functioning defined as premenstrual dysphoric disorder (PMDD). Clinically significant premenstrual symptoms occur in at least an additional 20% of menstruating women. The diagnosis of PMDD should be confirmed by prospective symptom charting over 2 menstrual cycles to confirm the timing of the symptoms and to rule out other diagnoses. The burden of illness of PMDD includes disruption of parenting and partner relationships and decreased productivity in work roles. In addition, women with PMDD have increased use of health care services such as clinician visits and increased use of prescription medications and over-the-counter preparations. The etiology of PMDD is multifactorial. In particular, dysregulation of the serotonin and allopregnanolone systems is implicated. Several effective treatment options exist, including serotonergic antidepressant medications and an oral contraceptive that contains ethinyl estradiol and drosperinone. In addition, other hormones that suppress ovulation, anxiolytics, cognitive therapy, chasteberry and calcium may be helpful.
Cinq pour cent des femmes menstruées ont des symptômes prémenstruels sévères et une incapacité du fonctionnement appelée trouble dysphorique prémenstruel (TDPM). Au moins 20 % de femmes menstruées de plus ont des symptômes prémenstruels cliniquement significatifs. Il faut confirmer le diagnostic de TDPM en suivant les symptômes de façon prospective au cours de deux cycles menstruels afin de confirmer le moment de l’apparition des symptômes et d’exclure d’autres diagnostics. Le fardeau morbide imposé par le TDPM comprend la perturbation des relations avec les enfants et le partenaire et une baisse de productivité au travail. Les femmes atteintes de TDPM ont en outre recours davantage aux services de santé comme les visites aux cliniciens et prennent davantage de médicaments d’ordonnance et en vente libre. L’étiologie du TDPM est multifactorielle. La dysrégulation des systèmes de la sérotonine et de l’allopregnanolone en particulier est mise en cause. Il existe plus d’un traitement efficace possible, y compris des antidépresseurs sérotoninergiques et un contraceptif oral qui contient de l’éthinyloestradiol et de la drosperinone. D’autres hormones qui bloquent l’ovulation, des anxiolytiques, la thérapie cognitive, le gattilier (Vitex agnus castus) et le calcium peuvent en outre aider.
Reproductive Affective Disorders: a Review of the Genetic Evidence for Premenstrual Dysphoric Disorder and Postpartum Depression
2017, Current Psychiatry Reports

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Investigation of transcription factor AP-2beta genotype in women with premenstrual dysphoric disorder

Abstract

Section snippets

Acknowledgements

Anal. Biochem.

Mech. Dev.

Neurosci. Lett.

Neurosci. Lett.

Neuropsychopharmacology

Dev. Biol.

J. Biol. Chem.

The epidemiology of perimenstrual psychological symptoms

Acta Psychol. Scand.

Tryptophan depletion increases aggression in women during the prementrual phase

Psychopharmacology

Polymorphisms of the human IFNG gene noncoding regions