Emin Erdal

Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome

Abstract. Fibromyalgia syndrome (FS) is associated with a neuroendocrinal disorder characterized by abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperactive adrenocorticotropic hormone (ACTH) release and adrenal hyporesponsiveness. Catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines and catecholamine-containing drugs. Polymorphism in the gene encodes for the COMT enzyme. For this study, the significance of COMT polymorphism was assessed in FS. There were three polymorphisms of the COMT gene: LL, LH, and HH. The analysis of COMT polymorphism was performed using polymerase chain reaction (PCR). Sixty-one patients with FS and 61 healthy volunteers were included in the study. Although no significant difference was found between LL and LH separately, the LL and LH genotypes together were more highly represented in patients than controls (P=0.024). In addition, HH genotypes in patients were significantly lower than in the control groups (P=0.04). There was no significant difference between COMT polymorphism and psychiatric status of the patients as assessed by several psychiatric tests (P>0.05). In conclusion, COMT polymorphism is of potential pharmacological importance regarding individual differences in the metabolism of catechol drugs and may also be involved in the pathogenesis and treatment of FS through adrenergic mechanisms as well as genetic predisposition to FS.

Association of T102C polymorphism of the 5-HT2A receptor gene with pyschiatric status in fibromyalgia syndrome

Abstract. Serotonin (5-HT) is a key neurotransmitter in the central nervous system. It is suggested that serotonergic dysfunction may be involved in the pathophysiology of fibromyalgia syndrome (FS). In this study, we aimed to investigate T102C polymorphism of the 5-HT2A receptor gene in FS. Fifty-eight patients with FS and 58 unrelated healthy volunteer controls were included in the study. In both groups, the C/C, C/T, and T/T genotypes of the 5-HT gene were represented in 31% (22.4% in controls), 50% (53.4%), and 19% (24.1%), respectively. The 5-HT2A receptor gene polymorphism results were not significantly different between patients and controls (chi squared test, P>0.05). There was a significant correlation between patients with the T/T genotype and the subgroup according to the SCL-90-R test, (analysis of variance, P<0.05). We also saw that patients with the T/T genotype had the lowest pain threshold. Conclusion. T102C polymorphism of the 5-HT2A receptor gene is not associated with the etiology of FS. Our results also indicate that the T/T genotype may be responsible for psychiatric symptoms of FS.

Association of the -1438G/A polymorphism of the 5-HT2A receptor gene with obstructive sleep apnea syndrome

Objective: Serotonergic neurons innervating motoneurons increase their firing rates in response to respiratory challenges, and long-term facilitation of respiratory activity in response to hypoxia is serotonin (5-HT) dependent. Polymorphism of the genes which code for 5-HT receptors may affect functions of the serotonergic system, and may be associated with obstructive sleep apnea syndrome (OSAS). The objective in this study was to assess the significance of T102C and –1438G/A polymorphisms of the 5-HT2A receptor gene in OSAS. Methods: Fifty-five patients with OSAS and 102 healthy volun teers were included for genetic analyses of T102C and –1438G/A polymorphisms of the 5-HT2A receptor gene. Results: For the T102C polymorphism, there was no significant difference between the patients and controls and both genders (p > 0.05). For the –1438G/A polymorphism, the A/A and G/A genotypes were overrepresented in the patients and controls, respectively (p = 0.045). In the control group, the genotypes of both genders were not significantly different (p > 0.05). In the patients, the A/A and G/A genotypes were overrepresented in males and females, respectively (p = 0.035). Concerning males, the A/A genotype was overrepresented in patients (p = 0.007). Conclusion: Serotonergic mechanisms appear to be related to OSAS. The T102C polymorphism of the 5-HT2A receptor gene is not associated with OSAS. However, the –1438G/A polymorphism is associated with OSAS occurrence, especially in male patients. This polymorphism may also be associated with different OSAS incidences of both genders.

The A218C polymorphism of tryptophan hydroxylase gene and migraine

OBJECTIVE To determine the significance of the A218C polymorphism of the tryptophan hydroxylase (TPH) gene in migraine. METHODS Fifty-nine migraineurs and 62 healthy controls were included in the study, and polymerase chain reaction - restriction fragment length polymorphism assays were used to determine TPH A218C polymorphism. RESULTS There was no association between TPH gene polymorphism and gender, family history of migraine and epilepsy, or aura. There was no significant difference between the allele frequencies of both groups (p>0.05). A significant difference was found between the genotypes of the migraineurs and controls regarding the AA genotype. Homozygosity for the C allele or heterozygosity for the A or C was not associated with the occurrence of migraine (p>0.05), but homozygosity for the A allele was less frequent in the migraineurs (p=0.02). CONCLUSION Since it is unlikely that TPH polymorphism alters serotonin biosynthesis, its association with migraine may be attributed to linkage disequilibrium with a functional variant within the TPH gene or a nearby gene.

Association of serotonin transporter gene-linked polymorphic region and variable number of tandem repeat polymorphism of the serotonin transporter gene in lichen simplex chronicus patients with psychiatric status

Background  The serotonin (5‐hydroxytryptamine; 5‐HT) is a key neurotransmitter in the central nervous system and a responsible mediator for the itch. Dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex neuropsychiatric diseases.