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Background. Polycythemia vera (PV) and essential thrombocytosis (ET) are hematological disorders characterized by excessive production of mature and functional blood cells. These cellular disorders are thought to be associated with impaired apoptosis, which is one of the major cellular death mechanisms in hematopoietic cells. Objectives. In this study, our objective was to examine the association between potential polymorphisms of the Bcl 2, Bax, Fas and Fas Ligand genes involved in apoptosis and the occurrence of PV and ET. Material and methods. A total of 93 patients diagnosed with PV (n = 38) or ET (n = 55) at the Department of Hematology were included in this study, and 93 healthy individuals served as controls. DNA isolation was performed in blood samples obtained from both groups of subjects to determine the Bcl 2, Bax, Fas, and Fas L genotypes using the real-time PCR method. Results. No statistically significant differences between controls and patients were found in terms of Fas -670 G > A (rs1800682), Fas -1377 G > A (rs2234767), Fas L IVS2 -124 A > G (rs5030772), Bax -248 G > A (rs4645878) and Bcl 2 -938 C > A (rs2279115) polymorphisms, genotypes, and allele frequency (p > 0.05). Conclusions. The results show that polymorphisms in the Bcl 2, Bax, Fas, and Fas Ligand genes involved in the apoptotic pathways may not play a role in the pathogenesis of PV and ET. [ABSTRACT FROM AUTHOR]

Objective: To investigate the neurometabolite level changes according to synapsin III gene rs133945G.A and rs133946C.G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). Methods: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel ¹H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. Results: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G.A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C.G polymorphism-CG genotypes (P=0.014). Both rs133945G.A and rs133946C.G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C.G polymorphisms after Bonferroni adjustment (P=0.016). Conclusion: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objective: Alcoholism is associated with genetic variants of genes related to alcohol metabolizing enzymes, dopaminergic, gamma-aminobutyric acidergic, glutamatergic, opioid, cholinergic, and serotonergic systems. Neurpeptide Y system and Neurexins were shown to be associated with alcohol dependence. Recent studies identified new genetic polymorphisms related to endogenous cannabinoid system, neuropetide Y and neurexin. In the present study, we aimed to investigate the association of Neurpeptide Y LEU7PRO rs16139 and neurexin 3 gene rs760288 polymorphisms with alcohol dependence in patients with alcohol dependence and healthy control subjects. Methods: 123 patients who were diagnosed with alcohol dependence according to the DSM-IV criteria and 159 healthy volunteers were included in the study. Blood samples were used to investigate polymorphisms. The genotyping of the neurexin 3 gene rs760288 and the neuropetide Y gene Leu7Pro rs16139 polymorphisms was performed using TaqMan SNP Genotyping Assays Real-Time PCR System. Results: Of the 2 genetic polymorphisms investigated in the present study, we detected association between and neurexin 3 gene rs760288 polymorphisms with alcohol dependence. Conclusions: Neurexin gene polymorphisms might be an important factor in development of alcohol addiction. [ABSTRACT FROM AUTHOR]

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods: Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at -18°C prior to analysis. Results: There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT gene polymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion: These results suggested that there was no significant relationship between PMS and COMT gene polymorphism. Since we could not find a direct correlation between the COMT gene polymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease. [ABSTRACT FROM AUTHOR]

Background: Excessive apoptosis is believed to play a role in many degenerative and non-degenerative neurological diseases including Alzheimer's disease (AD). Much recent data suggest that apoptotic mechanisms may represent the missing link between Aβ deposition and proteolysis of tau protein. However, there is emerging evidence that apoptotic mechanisms may play a role in Alzheimer's Disease pathogenesis in the absence of overt apoptosis. TNF-related apoptosis inducing ligand receptor 1 (Death Receptor 4, DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death. Aims: The aim of our study was to further investigate the relationship between genetic variants of DR4 and Alzheimer's Disease. Study Design: Case control study. Methods: Sixty-eight patients with AD were included in the study. The control group comprised 72 subjects without signs of neurodegenerative diseases, as evidenced by the examination. DNA was extracted from whole blood using the salting-out procedure. Genotypes were identified by restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) products. Results: We observed significant differences in the genotypic distribution of the rs6557634 polymorphism in AD patients compared with controls (p<0.05); our data suggest that the GA genotype in rs6557634 could be protective against AD (p<0.05). However, there were no significant differences between AD patients and control groups in terms of the DR4 rs20575 polymorphism (p>0.05) and the DR4 rs20576 polymorphism (p>0.05). According to haplotype analysis of the DR4 gene for rs6557634, rs20575 and rs20576 polymorphisms, GCA and GCC haplotypes might be a risk factor for AD. Also, we have shown that ACA, GGC and GGA haplotypes might be protective factors against AD. Conclusion: The present results indicate for the first time the possible contribution of the DR4 gene rs6557634, rs20575, rs20576 polymorphisms in Alzheimer's Disease, which may influence susceptibility to Alzheimer's Disease. [ABSTRACT FROM AUTHOR]

It was aimed to investigate the association of the synapsin III gene −196 G> A and −631 C>G polymorphisms that takes place in an encoding presynaptic protein, with adult attention deficit hyperactivity disorder (ADHD). One hundred thirty-nine patients having adult ADHD and 106 controls were included in the study. DNA samples were extracted from whole blood and genetic analyses were performed. A significant difference was determined between ADHD and synapsin III gene −631 C>G polymorphism compared to the control group. No significant difference was determined between ADHD and synapsin III gene −196 G>A polymorphism. These polymorphisms were found not to be associated with subtypes of ADHD. It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD. Association of synapsin III gene with adult attention deficit hyperactivity disorder. One of two polymorphisms in synapsin III studied was found to be associated with ADHD. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Neuropsychiatry / Nöropsikiyatri Arşivi is the property of Turkish Association of Neuropsychiatry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anatolian Journal of Psychiatry / Anadolu Psikiyatri Dergisi is the property of Anatolian Journal of Psychiatry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective. There are contrasting results obtained in migraineurs concerning the levels and the role of both pro-inflammatory and anti-inflammatory cytokines. In this study, the association of the occurrence and clinical characteristics of migraine with the polymorphisms of tumor necrosis factor α (TNF-α) −308 G/A (rs1800629), interleukin-1α (IL-1α) +4845 G/T (rs17561), IL-1β+3953 C/T (rs1143634) and interleukin-1 receptor antagonist variable number tandem repeat (IL-1RA VNTR) genes were studied. We also investigated the genetic linkage between these genes. Design, Setting, Patients. Sixty-seven patients with migraine without aura (MwoA) and 96 unrelated, age- and sex-matched migraine-free, healthy control subjects from the same geographic area were investigated. Results. We observed significant differences in the genotypic distribution of the TNF-α−308 G/A and IL-1β+3953 C/T polymorphism for migraineurs compared with controls ( P = 0.004). Frequency of the TNF-α−308 GG genotype was higher in the control group than MwoA group (82.1% vs 55.2%). Differences in the distribution of the allele frequencies were also observed, being the TNF-α−308 G allele overrepresented in control group and TNF-α−308 A allele in MwoA group. In addition, there was a significant increase of the IL-1β+3953 T allele in MwoA cases compared with controls ( P = 0.004). Conclusions. In conclusion, the present results indicate the possible contribution of TNF-α and IL-1β gene polymorphisms to migraine headache generation in MwoA patients. [ABSTRACT FROM AUTHOR]

Background: Long-term exposure to extremely low frequency magnetic fields (ELF-MFs) may be a risk factor for human cancer. One mechanism through which ELF-MFs could influence neoplastic development is the deletion/mutation of cancer-related genes. Cellular proliferation follows an orderly progression through the cell cycle, which is governed by different cyclins and cyclin-dependent kinase inhibitors (CDKIs). The putative tumor suppressor gene p18INK4C encodes a specific inhibitor of cyclin D-cyclin-dependent kinase 4 inhibitor complexes having an important role in cell-cyclin regulation. It has been found to be deleted/mutated in a variety of human cancers. Therefore, this study is to investigate whether or not long-term extremely low frequency electromagnetic field exposure may be a risk factor for human cancer due to the gene p18INK4C deletion/mutation. Methods: The study was carried out on 31 male electric workers and 30 healthy males between 30 and 40 years of age from the same geographic area and with similar lifestyles. We studied both groups by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Results: In comparison to the controls, band migration of exon 1 was found to be indifferent in all the subjects tested. However, only exon 2 of two electric workers was slow in migration with respect to both control and other subjects in the same class. This slow migration suggests that point mutations or polymorphisms may exist in this region of the p18INK4C gene. The relative risk (RR) for the unmatched analysis was 1,069 (95% confidence interval [CI] 0.975–1.172). Conclusions: The results suggest that long-term ELF-MFs exposure does not significantly increase the risk of cancer. [Copyright &y& Elsevier]

Disturbances in the serotonergic neurotransmission system have been implicated in the etiology of attenion deficit/hyperactivity disorder (ADHD). As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We previously demonstrated that the polymorphisms of the serotonin transporter gene promoter and regions of variable number of tandem repeats were involved in the pathogenesis of ADHD. The purpose of this study was to examine the relationship between ADHD and two polymorphisms (T102C and 1438 G/A) in the 5-HT2A gene in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 70 patients with ADHD and in 100 healthy controls. There was no significant difference between the frequencies of the T, C, G and A alleles of both groups. No association was found between the studied polymorphisms of the 5-HT2A gene and ADHD in this sample consisting of Turkish children. Overall, our results suggest that the investigated 5-HT2A polymorphisms are not major susceptibility factors in the etiology of ADHD.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine associations between interleukin ( IL ) -1A (+ 4845 ), IL-1B (+ 3954 ), and IL-1 receptor antagonist (RN) variable number tandem repeat polymorphisms and adverse pregnancy outcomes and periodontitis in a Turkish women. Design A total of 156 patients, including 64 women with normal birth outcome (NB) and 92 women with preterm/low birth weight outcome (PLBW) were included in this case-control study. Within 24 h after labor, maternal demographic characteristics and clinical periodontal parameters were recorded. The distribution and genotype frequencies of IL-1 were analyzed with polymerase chain reaction-restriction fragment length polymorphism assay. Statistical analyses were carried out for clinical periodontal parameters, genotype frequencies, and to identify explanatory variables for PLBW. Results PLBW was associated with maternal age ( p < 0.05), irregular prenatal care ( p < 0.001), previous PLBW ( p < 0.05), and antibiotic use during pregnancy ( p < 0.05). Measurements of probing depth and clinical attachment level (CAL) were significantly higher in the PLBW group than in the NB group ( p < 0.001). PLBW was associated with IL-1RN allele 2 ( p < 0.001). Moreover, stepwise logistic regression analysis showed that CAL (OR 1.39, 95% CI: 1.04–1.85) and IL-1RN polymorphism (OR 7.92, 95% CI: 2.76–22.79), previous PLBW (OR 5.01, 95% CI: 1.08–23.17), age (OR 1.22, 95% CI: 1.04–1.44) were predictors found to increase the risk of PLBW ( p < 0.05). There was a negative association between PLBW and regular prenatal care, total number of births, use an antibiotic during pregnancy period ( p < 0.05). Conclusion Our study showed that, IL-1RN allele 2, periodontal disease characterized with clinical attachment loss, previous PLBW and age could be an important risk factors for PLBW. [ABSTRACT FROM AUTHOR]

Aims: Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase ( MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase ( MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase ( MTHFD1) G1958A (rs2236225), reduced folate carrier ( RFC1) A80G (rs1051266), and cystathionine β-synthase ( CBS) 844ins68. Results: The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring ( p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS ( p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant. Conclusion: Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies. [ABSTRACT FROM AUTHOR]

The etiology of Parkinson's disease (PD), a neurodegenerative disorder, is still unknown and the role of genetic factors have been implicated. XRCC1 (X-Ray Repair Cross- Complementingin) protein is required for DNA single-strand break repair and interacts with poly-ADP-ribose-polymerase (PARP), DNA-ligase III and DNA polymerase beta. It has been shown by mouse models that PARP may have a role in the pathogenesis of various diseases including PD. The aim of the study is to investigate the association of PD with XRCC1 gene Arg399Gln polymorphism. Seventy-one unrelated PD patients (50 male, 21 female) and 76 healthy age and sex matched volunteers (53 male, 23 female) have been included in the study. Molecular analyses have been performed with Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. The relationship between the XRCC1 gene Arg399Gln polymorphism and the PD risk has been investigated with the binary logistic regression analysis. No statistically significant relation has been determined between the PD and control groups (p=0,364). The present study is the first research about the relationship between the DNA repair genes and PD in the literature and does not show any relationship between PD and XRCC1 gene Arg399Gln polymorphism in Turkish population. Further studies with larger sample sizes will reveal more information about the genetic polymorphisms in DNA repair genes for the risk and the etiopathogenesis of PD. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL). Materials and Methods: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs2DL1–4 and 2DS1–5 genes using polymerase chain reaction with sequence-specific primers. Results: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene–gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes. Conclusion: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Premenstrual syndrome (PMS) is characterized by recurrent psychological and/or somatic symptoms occurring specifically during the luteal phase of the menstrual cycle and resolving during menstruation. Premenstrual dysphoric disorder (PMDD) is the extreme, predominantly psychological end of the PMS spectrum, and it is estimated that 5-10% of regularly ovulating women experience PMDD. The cause of PMDD is unknown. Studies attempting to elucidate the pathophysiology of the syndrome concentrate on the hypothalamic-pituitary-adrenal (HPA) axis, the γ-aminobutyric acid (GABA) system, the serotonergic system, and the opioid system. The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions. Rs6280, also known as Ser9Gly, is a SNP in the dopamine receptor D3 DRD3 gene. Polymorphisms in the DRD3 gene have associations with schizophrenia, depression, and nicotine dependence. DRD3Ser9Gly polymorphism affected response to antidepressant treatment in major depressive disorder2. The endocannabinoid system is widely distributed throughout the brain and involved in mood and related disorders. Genetic polymorphisms of the endocannabinoid system have been explored in mental disorders3. There are currently two known subtypes of endocannabinoid receptors, termed CB1 and CB2. CNR1 polymorphisms were found to be associated with substance use disorders, depression, and anxiety disorders4. Rs1049353 and rs12720071 are common variants of the CNR1 gene. Carriers of an rs1049353(G) allele were less likely to respond favorably to antidepressant treatment, particularly if they were females with comorbid anxiety5. Since polymorphisms in DRD3Ser9Gly and CB1 receptors seemed to be associated with anxiety and depressive disorders, and as it is known that PMDD shares a range of characteristics with depressive and anxiety disorders, our aim was to investigate whether DRD3Ser9Gly and CB1 receptor polymorphisms are related to PMDD. METHODS: Study Population: Patients were recruited from consecutive applications to the Harran University Research Hospital obstetrics and gynecology outpatient clinic. The control group was selected from the staff of the Faculty of Medicine. Fifty-one patients with PMDD and 51 healthy control subjects between the ages of 18 and 45 were included in this cross-sectional study. Anyone having an existing Axis I psychiatric disorder according to the DSM-4 criteria was excluded from the study. Clinical diagnosis was determined according to DSM-IV. Control subjects reported no significant premenstrual symptoms. All subjects were evaluated with a semi-structured interview form to determine their sociodemographic features. This form also evaluates the symptoms of Premenstrual Syndrome (PMS), family history of PMS, and nicotine use. Clinical categorization of PMDD patients and control subjects was determined by prospective symptom rating with the use of the Daily Record of Severity of Problems (DRSP) scale-short form. Procedures: Venous blood samples were collected in EDTA-containing tubes. DNA was extracted from peripheral blood leukocytes by salting-out procedure. Genotypic Analysis of the Dopamine Receptor D3 (DRD3) Gene Ser9Gly(rs6280) Polymorphism: Genotypes were determined using a TaqMan™ fluorogenic 5'-nuclease assay with TaqMan Probes. All reactions were carried out following the manufacturer's protocol. Genotypic Analysis of CNR1 1359 G>A (codon Thr453Thr, rs1049353) Polymorphisms: The genotyping of CNR1 1359 G>A (codon Thr453Thr, rs1049353) polymorphisms was performed using predesigned TaqMan SNP Genotyping Assays (Applied Biosystems, Foster City, CA). The Assays-on-Demand SNP genotyping kit was used for the polymerase chain reaction (Applied Biosystems). Single nucleotide polymorphism amplification assays were performed according to the manufacturer's instructions. All procedures were conducted in a manner blind to the case status and other characteristics of the participants Statistical Analysis: Χ2 tests were performed to assess conformity to Hardy-Weinberg equilibrium and to detect any association between each genotype distribution and clinical category. Statistical significance was considered at exact probability values of p<0.05. RESULTS: Fifty-one patients with PMDD (age range: 20-46; mean: 30.2) and 51 healthy control subjects (age range: 15-44; mean: 28.0) were included in the study. There was no significant difference in age, BMI, height, weight, or number of children between PMDD group and controls except for marriage rates. 5.9% of PMDD patients were single, against 29.4% of the controls. Allele and genotype frequencies were not different between PMDD patients and controls in DRD3Ser9Gly polymorphism (Χ2: 0.356 and p: 0.837). Allele and genotype frequencies were not different between PMDD patients and controls in CNR1 polymorphism. Genotypes have Hardy-Weinberg equilibrium in DRD3Ser9Gly in the PMDD group (chi-square value=1.65 with 1 DF) but the other genotypes are not in Hardy-Weinberg equilibrium. There was no significant difference of DRD3Ser9Gly polymorphism between PMDD patients and controls. Similarly, there was no significant difference of CNR1 polymorphism between PMDD patients and controls. DISCUSSION: We genotyped the DRD3Ser9Gly (rs6280) and CNR1 polymorphisms in two groups of regularly ovulating women, one group with clinically diagnosed premenstrual dysphoric disorder and one group of normal healthy controls with no symptoms of premenstrual dysphoria. We found no association of DRD3Ser9Gly (rs6280) polymorphisms in PMDD. The D3 receptor is a candidate for being involved in mental disorders. Polymorphisms in the DRD3 gene have been studied in various psychiatric disorders. In a study of 88 patients being treated for schizophrenia with olanzapine, those who were rs6280(C;C) homozygote had greater positive symptom remission as compared with (C;T) or (T;T) genotypes. The ser9gly polymorphism has been associated with depression in different studies. A preliminary study showed that DRD3Ser9Gly polymorphism affected response to antidepressant treatment in major depressive disorder. Pharmacogenetic studies have reported that DRD3ser9gly polymorphism influenced antidepressant response in bipolar disorder patients treated with a combination of olanzapine and fluoxetine. Our first finding is the lack of an association of DRD3ser9Gly polymorphism in PMDD, and there is no other study looking for this association. As the etiology of PMDD is multifactorial, dopaminergic pathways may not be solely responsible in the pathophysiology of PMDD. Our second finding is a lack of association between CNR1 polymorphism and PMDD. The endocannabinoid system has been implicated in the pathogenesis of depression and anxiety. Patients with depression are found to have reduced levels of circulating endocannabinoids, and an up-regulation of CB1R was observed in the prefrontal cortex of subjects with major depression who died by suicide. Since While polymorphism (rs1049353) is associated with depression and anxiety, we did not find an association between CNR1 polymorphism (rs1049353) and PMDD. The endocannabinoid system may not be the sole responsible in the pathophysiology of PMDD. Previous genetic studies in premenstrual dysphoric disorder were mostly concerned with the serotonergic and noradrenergic systems. To our knowledge, this study is the first reported genotypic analysis of DRD3Ser9Gly (rs6280) and CNR1 polymorphisms in premenstrual dysphoric disorder. There may be several explanations for our negative findings. First, clinical categorization of patients with PMDD can be difficult because of the subjective nature of symptom interpretation. A second limitation is the possibility of population stratification. In studies comprising subjects taken primarily from a localized community, it is important to include healthy controls to determine typical genotype and allelic frequencies, although these may not be representative of the wider population. Third, the lack of association between the DRD3Ser9Gly (rs6280) and CNR1 polymorphisms and PMDD may be affected by sample size. We were unable to identify either a single genetic marker or a combined polymorphic profile for susceptibility to PMDD. However, it is the first study evaluating DRD3Ser9Glyand CNR1 polymorphisms in PMDD. It is not plausible to expect a single polymorphism to be the sole factor responsible for PMDD. It is likely that PMDD is a polygenic disorder, but the relative contributions of the various implicated genes are unknown. Cautious interpretation of the present study is warranted, both by the preliminary nature of these findings and by their basis in simple association analysis. The polymorphisms that were studied here do not represent major risk factors for PMDD. Confirmation of our findings will require independent validation in a larger group of subjects. [ABSTRACT FROM AUTHOR]