M. Emin Erdal

Serotonin transporter gene polymorphism in irritable bowel syndrome

OBJECTIVES:Serotonin is a key mediator of intestinal peristalsis, and after it is secreted, it is effectively cleansed from the neuronal gap by means of a high affinity substance called serotonin transporter (SERT), which depends on the Na+ and Cl− ions localized in the presynaptic neuronal membranes. The aim of this study was to investigate SERT polymorphism in patients with irritable bowel syndrome (IBS).METHODS:SERT gene polymorphism was assessed by polymerase chain reaction on DNA chains obtained from leukocytes in serum samples from 54 patients diagnosed with IBS and 91 healthy subjects. The polymorphism of two regions (variable number tandem repeats and the SERT gene—linked polymorphic region [5-HTTLPR]) of SERT was assessed.RESULTS:SERT polymorphisms were found to be similar in healthy subjects and IBS patients (p > 0.05). IBS patients were divided into three groups: diarrhea predominant (n = 18), constipation predominant (n = 26), and alternating diarrhea and constipation (n = 10). These groups were compared with respect to gene polymorphism, and it was found that the 5-HTTLPR allele S/S genotype occurred with greater frequency in the constipation predominant group than in the other two subgroups (p < 0.05), and L/S genotype frequency in the diarrhea predominant group was higher than those in the constipation and control groups.CONCLUSIONS:No relationship was found between IBS and SERT gene polymorphism. It is conceivable that the presence of the S/S genotype in IBS patients carries an increased risk of the constipation predominant type of IBS, whereas the presence of the 5-HTTLPR allele L/S genotype carries an increased risk of the diarrhea predominant type.

Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and prognosis.

Catechol‐O ‐methyltransferase (COMT) gene has long been implicated to play a role in the pathogenesis of schizophrenia. The aim of this study is to assess the relationship of schizophrenia and its subgroups with COMT gene polymorphism. We have attempted to evaluate a possible correlation between the severity and prognosis of the illness (the psychopathology of symptoms) and COMT gene polymorphisms. The study comprised 129 unrelated subjects who strictly met DSM‐IV criteria for schizophrenia, and 65 healthy unrelated controls. All subjects were of Turkish origin. A clinical evaluation of all patients was accomplished by applying the Brief Psychiatric Rating Scale (BPRS) test. The analysis of COMT polymorphism was performed using the polymerase chain reaction technique. Regarding COMT gene polymorphisms, no statistically significant difference was found between schizophrenic patients and control subjects. However, within the schizophrenic group, the average of BPRS points of patients with the L/L genotype was significantly higher than those of the L/H and H/H genotypes (F  = 6.25, degrees of freedom = 2, P  = 0.003). Although no statistically significant difference was found between the duration of illness and COMT variations, a higher frequency of hospitalization was found in patients with the L/L genotype compared with other groups (t  = 3.048, P  = 0.003). In conclusion, the findings indicate that COMT gene polymorphisms were not statistically significant between patient and control groups. However, the patients with the L/L genotype may have much more severe clinical signs in Turkish schizophrenics. COMT variations, however, do not help to evaluate the susceptibility of the patients, but can help in the estimation of severity of clinical manifestations. Further studies are required to better understand the association of symptomatology of schizophrenia and other psychiatric disorders with COMT gene polymorphism.

Significance of the catechol-O-methyltransferase gene polymorphism in migraine

The objective was to assess the significance of the catechol-o-methyltransferase (COMT) enzyme polymorphism in migraine. For this reason, 62 migraineurs and 64 healthy volunteers were included in the study. The analysis of COMT polymorphism was performed using PCR. The H/H genotype was more frequent in the control group than in the patients group (P=0.032). The homozygous or heterozygous L allele was over represented in the migraineurs compared with the controls (P=0.013). The L/L genotype was over represented in the migraineurs who also had a family history of migraine (P=0.003). There was no relationship between aura and COMT genotypes. In conclusion, the COMT polymorphism may be of potential pharmacological importance regarding the individual differences in the metabolism of catechol drugs in migraineurs. Although altered catecholamine activity due to polymorphism of COMT gene may be one of the mechanisms involved in the pathogenesis of migraine, these mechanisms are not related to presence or absence of aura.

Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene >

BACKGROUND The pathophysiology of tardive dyskinesia (TD) is not completely understood.Aim. - To assess the relationship of TD with 5-HT2A receptor gene, serotonin transporter gene (5 HTT), and catechol-o-methyltransferase (COMT) gene polymorphisms. METHOD Our study comprised 111 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and 32 TD, and 79 healthy unrelated controls; all the subjects were of Turkish origin. The analyses of 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were performed using polymerase chain reaction (PCR) technique. RESULTS The polymorphisms of these genes were not significantly different between the schizophrenic patients, TD and control subjects. CONCLUSION Our findings indicated that 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were similar in schizophrenia with non-TD, schizophrenia with TD, and healthy controls. These polymorphisms, though, do not help to evaluate the susceptibility to TD.

Association of the T102C polymorphism of 5-HT2A receptor gene with aura in migraine.

OBJECTIVE To find out the significance of the 5-HT2A receptor gene polymorphism in migraine. STUDY DESIGN A PCR study in which 61 migraineurs and 44 healthy controls were included. METHODS The T102C polymorphism of the 5-HT2A receptor gene was studied. The results of the migraineurs and controls were compared. The relationship between the gene polymorphism and aura was also assessed. RESULTS The representations of the 5-HT2A genotypes were similar in migraineurs and controls (p>0.05) as well as in the male and female migraineurs (p>0.05). The family history of migraine did not associate with 5-HT2A receptor gene polymorphism (p>0.05). There was a significant relationship between the presence of C/C genotype and migraine with aura (p=0.02) while C/T and T/T genotypes were over represented in the patients with migraine without aura (p<0.01). CONCLUSION The T102C polymorphism of the 5-HT2A receptor gene is not directly related to the increased risk of migraine. The associations between the genotypes of this gene and aura may suggest that 5-HT2A receptor gene polymorphism may be involved in determining the subtypes of or accompanying symptoms in the migraine disease.

T102C and -1438 G/A polymorphisms of the 5-HT2A receptor gene in Turkish patients with obsessive-compulsive disorder.

OBJECTIVE This study aimed to investigate the possible association between T102C and -1438 G/A polymorphism in the 5-HT2A receptor gene and susceptibility to and clinical features of obsessive-compulsive disorder (OCD). METHOD Fifty-eight patients with OCD and 83 healthy controls were included in the study. All patients were interviewed and rated by Yale-Brown Obsessive-Compulsive Scale. T102C and -1438 G/A polymorphisms of 5-HT2A receptor gene were determined by PCR technique in DNAs of peripheral leucocytes. RESULTS OCD patients and healthy controls did not show significant differences in genotype distribution for both polymorphisms investigated. We found that frequencies of the TT genotype for T102C polymorphism and the AA genotype for -1438 G/A polymorphism were significantly higher in patients with severe OCD compared to those with moderate or moderate-severe OCD. CONCLUSION The -1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with an increased risk of OCD. Our data suggest that the TT genotype of T102C and the AA genotype of -1438 G/A polymorphism might be a factor in clinical severity of OCD.

FSHR Single Nucleotide Polymorphism Frequencies in Proven Fathers and Infertile Men in Southeast Turkey

The influence of FSH receptor (FSHR) variants on male infertility is not completely understood. The present investigation is the first screening study for SNP at nucleotide position −29 in the core promoter region and codon 680 in exon 10 of the FSHR and the effect of the serum levels of FSH on male infertility in Southeast Turkey. The SNPs in codon 680 and at position −29 of the FSHR gene were analyzed by PCR-RFLP technique in 240 men with proven fathers, and 270 infertile men (150 nonobstructive azoospermic and 120 severe oligozoospermic). The separate analysis for SNP at nucleotide position −29 did not show any difference in genotypic frequencies and serum FSH levels. The genotype distribution of SNP at position 680 was different but does not influence serum FSH levels. Together the two SNPs form four discrete haplotypes (A-Thr-Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A statistically significant difference in the allelic distribution of G-Asn/G-Ser and G-Ser/G-Ser genotype between proven fathers and infertile men but there were not any statistically significant difference in the overall frequency of the four FSHR haplotypes. We conclude that the FSHR haplotype does not associate with different serum FSH levels but it is differently distributed in proven fathers and infertile men.

Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine‐to‐glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist.

Significance of catechol-O-methyltransferase gene polymorphism in myofacial pain syndrome

AbstractThe objective was to investigate possible association of the catechol o-methyl transferase (COMT) gene polymorphisms with myofacial pain syndrome (MFPS). The polymorphism of the COMT gene was compared between 49 patients with MFPS and 113 control subjects. Relationship between COMT polymorphism and psychiatric status of the patients was also assessed using SCL-90-R, BDS, and STAI-I and II tests. A PCR-based restriction fragment length polymorphism assay was used to detect G → A transition at position 1947 in COMT. There was no relationship between MFPS and COMT polymorphism (p > 0.05). The patients who had MFPS without any temporomandibular joint problem had significantly higher expression of LL genotype when compared to those with joint problems (p 0.05). In conclusion, MFPS is not related to COMT polymorphism. COMT polymorphism is not associated with the psychiatric status of the patients. COMT polymorphism m...

Lack of Association Between the C276T Polymorphism of the Neuronal Nitric Oxide Synthase Gene and Migraine

ABSTRACT A migraine attack is a spectacularly complex brain event that can produce a wide array of neurological and systemic symptoms. The molecular mechanisms and genetics of migraine have not yet been clarified. The objective of this study was to analyze the genotype distributions and allele frequencies for the C276T polymorphism of the neuronal nitric oxide synthase (nNOS) gene among the patients with migraine. The diagnosis of migraine was made clinically based on questionnaires. One hundred and twenty patients with migraine were genotyped for the C276T polymorphism of the nNOS gene and compared with 185 age-matched healthy controls. Genomic DNA from migraine patients and controls was analyzed by polymerase chain reaction (PCR). A PCR–restriction fragment-length polymorphism analysis of nNOS gene polymorphism was performed, and the results were compared. Neither genotype distributions nor the allele frequencies for the C276T polymorphism showed a significant difference between the groups. Additionally, there was no marked differences in genotype distribution or allele frequencies for the migraine without aura and migraine with aura subgroups when compared to control group. These results suggested that migraine of the Turkish population seemed to develop without any alterations in nNOS C276T polymorphism. Our data showed that there is no marked association between the C276T polymorphism of the nNOS gene and migraine.