Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism.

1. Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS. 2. The study included 379 FMS patients and 290 controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. 3. The genotype frequencies of Val158Met polymorphism showed a small difference between FMS patients and healthy controls (p = 0.047), however, the Met/Met genotype was significantly higher in FMS patients than healthy controls (p = 0.016). No difference was observed for allele frequencies between two groups. Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud's syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p = 0.037, p = 0.042, p = 0.039 and p = 0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p = 0.017). 4. The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.

Polymorphism of catechol-o-methyltransferase and uterine leiomyoma.

Uterine leiomyoma (ULM) is the most common gynecological benign tumor that is affecting around 20-50 % of women over the age of 30. Although its molecular pathogenesis is still unknown, ULM has a multifactorial etiology determined by both genetics and environmental factors. The present study was designed to find out whether Val158Met polymorphism in the catechol-o-methyltransferase (COMT) gene is associated with the risk of ULM. We analyzed COMT Val158Met polymorphism in 105 ULMs patients and 105 healthy subjects using a polymerase chain reaction-based restriction fragment length polymorphism assay. We found remarkably similar frequencies in ULM compared with controls for COMT Val158Met genotypes and alleles, and no association was found between ULM and this polymorphism (p = 0.46). The COMT 158 Met allele in patients with large (≥5 cm) fibroids was higher than in patients with small (<5 cm) fibroids, and significant association was found between fibroid size and COMT 158 Met allele (p = 0.011, OR 0.50, 95 %CI 0.28-0.90). Our results reflect that COMT Val158Met polymorphism is not associated with an increased risk of ULMs, but Val158Met polymorphism may be a risk factor for development of large fibroids in Turkish patients with ULM.

Genetic variations in tumor necrosis factor alpha, interleukin-10 genes, and migraine susceptibility.

OBJECTIVES: Migraine is a very common headache disorder and pathogenesis of the disease is still largely unknown. Cytokine genes have been implicated in migraine susceptibility. The present study was designed to explore the associations of polymorphisms in the tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) gene, and IL-10 haplotypes in Turkish migraine patients. METHODS: TNF-α-308G/A, IL-10 -1082G/A, -819C/T, and -592C/A polymorphisms in 203 migraine patients and 202 healthy subjects were analyzed by using amplification refractory mutation system-polymerase chain reaction. RESULTS: The -308G/A genotypic and -308A allelic frequency of TNF-α polymorphism was higher in migraine patients than healthy controls, and significant association was found between migraine and TNF-α-308G/A polymorphism (Bonferroni correction [Pc]: <0.0001, odds ratio: 2.16, 95% confidence interval: 1.44-3.28). No statistically significant association was found between IL-10 -1082G/A, -819C/T, and -592C/A polymorphisms and haplotypes containing these alleles and migraine. CONCLUSIONS: This study reflect that TNF-α-308G/A polymorphism may be one of the many genetic factors for migraine susceptibility in the Turkish population.

Analysis of dopamine beta hydroxylase gene polymorphisms in migraine.

BACKGROUND: Migraine is a complex neurological disorder characterized by severe recurrent headache, nausea, vomiting, photophobia, and phonophobia. The frequency and duration of these symptoms varies among individuals. Dopaminergic systems are believed to be involved in migraine pathophysiology. We aimed to look for association of polymorphisms in dopaminergic genes in genetic susceptibility to migraine in Turkey population. METHODS: The present study was designed to explore possible association of three polymorphisms, (1021C>T (Rs1611115), +1603C>T (Rs6271; C535R) and +444G>A (rs1108580), of Dopamin Beta Hydroxylase gene in migraine patients. 200 migraine patients and 267 healthy controls were included in the study. Genomic DNA was extracted from blood and genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism methods (PCR-RFLP). RESULTS: Statistical evaluation of data results showed a significant association for allelic and genotypic frequency distribution between the Dopamin Beta Hydroxylase gene +1603C>T polymorphism and migraine (p=0.000, OR: 4.36, 95% CI: 2.73-7.16). There was no association observed between the -1021C>T and +444 G>A polymorphisms of the Dopamin Beta Hydroxylase gene and migraine (p=0.8731 and p=0.7584). CONCLUSIONS: This study reflects that Dopamin Beta Hydroxylase gene +1603C>T polymorphism may be one of the many genetic factors for migraine susceptibility in the Turkish population.

MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia.

CONCLUSION: A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4 G/C) and MBL2 C + 4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia. AIM: This study aimed to investigate the relationship of SLC11A1, MBL, and P2X7 gene polymorphism with oropharyngeal tularemia. METHODS: The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5'(GT)n Allele 2/3, Int4 G/C, 3' UTR, D543N G/A), MBL (MBL2 C + 4T (P/Q), and P2X7 (-762 C/T and 1513 A/C). RESULTS: Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p = 0.006 and OR = 1.96 (1.21-3.20)). An association was detected between MBL2 C + 4T (P/Q) gene polymorphism and oropharyngeal tularemia (p < 0.005 and OR = 0.30 (0.19-0.48)). No significant relation was found between P2X7 (-762 C/T and 1513 A/C) gene polymorphism and oropharyngeal tularemia in this study (p > 0.05).

High association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Oral ulcers are also the most common feature of Behçet's disease (BD). Association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with BD has been reported in Turkish population. The aim of the present study was to investigate the possible association between ACE gene I/D polymorphism and RAS, and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients. The study included 198 patients affected by RAS and 214 healthy controls. ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction with I and D allele-specific primers. The genotype and allele frequencies of I/D polymorphism showed statistically significant differences between RAS patients and controls (p < 0.0001 and p < 0.0001, respectively). After stratifying RAS patients according to clinical and demographical characteristics, no significant association was observed. In conclusion, the results of this study suggest that I/D polymorphism of the ACE gene was positively associated with predisposition to develop RAS in Turkish population. Further studies with larger populations are recommended.

Genetic association of 5-HT1A and 5-HT1B gene polymorphisms with migraine in a Turkish population.

Migraine, a very common headache disorder, is regarded as a polygenic disease and serotonergic pathways appear to play a major role in its pathogenesis. The present study was designed to explore the associations of polymorphisms of 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A) and 5-hydroxytryptamine receptor 1B (5-HT1B) genes in Turkish migraine patients. 5-HT1A C-1019G (rs6295) promoter and 5-HT1B G861C (rs6296) exon polymorphisms in 203 migraine patients and 202 healthy subjects were analyzed by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele and genotype frequencies were not significantly different between migraine patients and healthy subjects for both the 5-HT1A C-1019G promoter and 5-HT1B G861C exon polymorphisms. Our data do not support the hypothesis that 5-HT1A C-1019G and 5-HT1B G861C polymorphisms have effects on migraine.

Functional polymorphisms in cell death pathway genes FAS and FAS ligand and risk of alopecia areata.

FAS and FAS ligand (FASLG) are important proapoptotic proteins that have a significant function in regulating cell growth and apoptosis and play essential roles in many human autoimmune diseases. Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease mediated by T cells to the hair follicles. The concept of an autoimmune mechanism as the basis for AA led us to investigate a possible association between the FAS and FASLG polymorphism with AA susceptibility and disease progression on AA patients in Turkish population. The study group consisted of 118 unrelated patients with AA and 118 unrelated healthy controls. We genotyped FAS-670 A/G and FASLG-124 A/G polymorphisms and assessed their association with AA risk. A statistically significant difference was observed between patients and controls according to genotype frequencies of FAS gene (p = 0.0002). GG genotype of 670 A/G polymorphism was found to be protective against AA (p = 0.000, OR 0.07, 95 % CI 0.00-0.41). It can be concluded there is a reduced risk of AA risk appeared to be associated with FAS-670 A/G. No association was observed between AA patients and controls according to genotype and allele distribution of FASLG gene 124 A/G polymorphism (p = 0.1297, p = 453, respectively). In conclusion, we provide evidence that FAS/FASLG polymorphisms may have an effect on the risk of AA in the Turkish population. These findings provide an additional support to a genetic basis for AA development.

Association between 1603C>T polymorphism of DBH gene and bipolar disorder in a Turkish population.

OBJECTIVES: Dopamine-ß-hydroxylase (DBH) is the enzyme responsible for the conversion of dopamine (DA) to norepinephrine (NE, noradrenaline) which is a key neurotransmitter in the central and peripheral nervous systems. Bipolar disorder is a major psychiatric disorder. The present study was designed to explore the associations of polymorphisms of DBH gene in Turkish patients with bipolar disorder. METHODS: -1021C>T (rs1611115) polymorphism in promoter region, 444G>A (rs1108580) polymorphism in exon 2 and 1603C>T (rs6271; C535R) polymorphism in exon11 of DBH gene were analyzed in 106 patients with bipolar disorder and 106 healthy subjects by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The results showed statistically significant associations for genotypic and allelic distribution between the 1603C>T polymorphism and bipolar disease (p=0.0012 and p=0.034, respectively). There was no association observed between the genotype and allelic frequencies for -1021C>T and 444G>A polymorphisms and bipolar disorder. CONCLUSIONS: Our data suggests that the 1603C>T polymorphism of the DBH gene is associated with susceptibility to bipolar disorder in a Turkish population.