Significance of serotonin transporter gene polymorphism in tinnitus.

OBJECTIVES: To assess the role of serotonin transporter gene (SLC6A4) polymorphism in tinnitus. MATERIALS AND METHODS: Fifty-four consecutive patients experiencing subjective tinnitus and 174 healthy controls were allocated for the study. Psychoacoustic parameters of tinnitus were measured. Beck Depression Inventory was used to assess the depression level of the patients. Tinnitus Handicap Inventory was used to assess the severity of tinnitus. A visual analog scale was designed to measure the impact of tinnitus on quality of life of the patients. The 44-bp insertion-deletion in the promoter region (5-HTTLPR) and 17-bp variable number tandem repeats in the second intron of the serotonin transporter gene were assessed. RESULTS: No difference was found between the genotypes and allele frequencies of the patients and controls regarding variable number tandem repeats and 5-HTTLPR polymorphisms (p > 0.05). There was no association between the psychoacoustic parameters of tinnitus and SLC6A4 polymorphism (p > 0.05). There was a significant association between the 5-HTTLPR polymorphism and scores from the visual analog scale of the patients (p < 0.05). CONCLUSION: Generation of tinnitus signal is not associated with SLC6A4 polymorphism and possibly with serotonergic mechanisms. However, the "ll" genotype variant of the SLC6A4 polymorphic promoter region seems associated with the limbic and autonomic nervous system symptoms of the patients with tinnitus. Therefore, serotonergic mechanisms may help explain the neurophysiological model of tinnitus, and serotonin replacement or serotonin reuptake inhibitors may increase the success rate of tinnitus treatment modalities based on the neurophysiologic model of tinnitus.

Role of nitric oxide synthase gene intron 4 and exon 7 polymorphisms in obstructive sleep apnea syndrome.

The objective of our study was to assess the association of eNOS4 and eNOS296 polymorphisms of endothelial nitric oxide synthase (eNOS) gene with obstructive sleep apnea syndrome (OSAS). Forty-eight patients with OSAS and 181 healthy volunteers were included in the study. Genotype analyses were performed for eNOS intron 4 VNTR and exon 7, Glu298Asp (G --> T) polymorphisms. There was no significant difference between the patients and controls regarding eNOS4 polymorphism (P > 0.05). There was a significant difference between the patients and controls regarding eNOS296 polymorphism. Glu/Asp variant was more frequent whereas Glu/Glu variant was less frequent in the patients compared to controls (P < 0.001). There was no relationship between eNOS4 and eNOS296 polymorphisms and polysomnography parameters, apnea-hypopnea index, age, gender, body weight and height, body mass index, hypertension, coronary artery disease, arrhythmia, diabetes mellitus, hypercholesterolemia and smoking (P > 0.05). The eNOS4 polymorphism of NOS gene is not associated with OSAS. However, eNOS296 polymorphism of NOS gene is associated with occurrence of OSAS, but not with severity of OSAS.

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. OBJECTIVES: The purpose of this study was to evaluate the relationship between lichen simplex chronicus and dysfunction and serotonin transporter (5-HTT) gene polymorphism. METHODS: Thirty-nine patients with lichen simplex chronicus and 61 healthy control subjects were examined. RESULTS: The results for the patients and control subjects were not significantly different (P > 0.05) in long/long (L/L) and long/short (L/S) genotypes of 5-HTT gene-linked polymorphic region (HTTLPR) polymorphism, but short/short S/S genotype was lower in lichen simplex chronicus patients (17.9%) than in controls (42.6%). This difference was statistically significant (P = 0.028). The results for the patients and control subjects were not significantly different in 12/12, 10/12 and 10/10 genotypes of variable number of tandem repeat (VNTR) polymorphism (P > 0.05). Beck depression inventory (BDI) scores and symptom checklist-90-revised (SCL-90) psychotic subscale were overrepresented significantly in the 12/12 genotypes than 10/12 genotypes. State and Trait Anxiety Inventory tests (STAI-I and -II) point averages were not statistically significant (P > 0.05) CONCLUSION: S/S genotypes of HTTLPR polymorphism in the 5-HTT gene may be related to lichen simplex chronicus and that patients who have 12/12 genotypes of VNTR polymorphism may be affected psychiatrically.

Which genotype of MAO gene that the patients have are likely to be most susceptible to the symptoms of fibromyalgia?

The objective of this study was to analyze the genotype distributions and allele frequencies for the MAO-A and MAO-B polymorphism of the MAO gene among the patients with fibromyalgia syndrome (FS). One hundred and seven fibromyalgia patients and 90 unrelated healthy subjects were included into the study. Genomic DNA of 107 FS patients and 90 healthy control subjects were analyzed by polymerase chain reaction. Polymorphism of the MAO gene was: 1-1, 1-3, 3-3, 3-4. The "allele 3" had a 2.7 to 4.8-fold increased transcription activity than the "allele 1". The frequencies of the genotypes of the patients with FS and healthy controls were compared. Although no significant difference was found in genotypes of patients and controls (P = 0.0559), it is likely that "allele 3" could be a more riskful factor for FS than "allele 1" (P = 0.033). Fibromyalgia impact questionnaire was administered to FS group as well as control group. One of our findings is that, the patients whose genotype 3-3 may be mostly affected by the symptoms of FS. In conclusion, it seems plausible to say that MAOA-dependent metabolism of the biological amines may be partly related to high-activated MAO-A, allele 3, in the occurrence of FS among Turkish population.

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.

PPAR-gamma2 Pro12Ala polymorphism is associated with weight gain in women with gestational diabetes mellitus.

OBJECTIVE: The polymorphisms of peroxisome proliferator-activator receptor-gamma2 (PPAR-gamma2) have been suggested to affect glucose metabolism and weight gain. Both conditions show great variations during pregnancy that makes pregnancy a suitable condition to detect any metabolic abnormalities related to PPAR-gamma2 polymorphisms. The objective of this study is to investigate the prevalence and metabolic impacts of PPAR-gamma2 polymorphism in control pregnant women and in patients with gestational diabetes mellitus (GDM). METHODS: In this case-control study, anthropometric and metabolic variables of 100 non-diabetic pregnant women and of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test (OGTT) were compared on the basis of PPAR-gamma2 polymorphism by univariate analysis of covariance. RESULTS: There were no statistically significant differences in baseline characteristics and the mean 50 g glucose challenge test values of pregnant women in both groups on the basis of PPAR-gamma2 genotype, although patients with Pro12Ala polymorphism were significantly taller in GDM group. The Pro12Ala polymorphism had no effect on 100 g OGTT results of patients with GDM. However, patients with GDM who had Pro12Ala polymorphism gained significantly more weight during their pregnancy. CONCLUSION: The PPAR-gamma2 Pro12Ala polymorphism was observed to have no effect on glucose metabolism in normal pregnant women and women with GDM. However, only the patients with GDM who had this polymorphism gained significantly more weight during their pregnancy. It seems that Pro12Ala polymorphism plays a dynamic and interactive role in the regulation of BMI and glucose homeostasis.

Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus.

OBJECTIVE: Insulin receptor substrate-1 (IRS-1) expression and tyrosine phosphorylation is decreased during pregnancy. Pregnancy may be a suitable condition to detect any abnormalities related to IRS-1 polymorphisms. Therefore, we aimed to investigate the prevalence and metabolic impacts of IRS-1 G972R polymorphism in patients with gestational diabetes mellitus (GDM). STUDY DESIGN: Anthropometric and metabolic variables of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test were compared on the basis of IRS-1 polymorphism by univariate analysis of covariance. RESULTS: Patients with IRS-1 G972R were more obese at the beginning of pregnancy, had higher serum fasting insulin and glucose levels. Weight gain during pregnancy and insulin and glucose levels after glucose ingestion was comparable between groups. CONCLUSION: IRS-1 G972R was associated with the baseline characteristics of the patients with GDM, and might be related to insulin resistance that is seen in obese patients with GDM.

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.

Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic features in women with polycystic ovary syndrome.

OBJECTIVE: To examine the prevalence and the effects of Gly972Arg (G972A) variant of insulin receptor substrate-1 (IRS-1) in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: An academic clinical research center. PATIENT(S): Sixty women with PCOS and 60 control women matched for age. INTERVENTION(S): Biometric measures, metabolic and hormonal measures, genetic analyses. MAIN OUTCOME MEASURE(S): Serum androgens, glucose, and insulin were measured. Blood leukocytes were used for genetic analyses. RESULT(S): The G972A variant was encountered more often in women with PCOS. The G972A carriers were more obese than their counterparts, had higher fasting insulin levels, and were more insulin-resistant. However, androgen levels did not differ on the basis of IRS-1 genotype. CONCLUSION(S): We observed that the G972A variant of IRS-1 was more prevalent in women with PCOS, and that it had important metabolic effects without having a direct effect on the androgen levels. However, the G972A variant of IRS-1 may modulate reproduction by lowering sex hormone-binding globulin in both healthy women and women with PCOS.

Association of the -1438 G/A and 102 T/C polymorphism of the 5-Ht2A receptor gene with irritable bowel syndrome 5-Ht2A gene polymorphism in irritable bowel syndrome.

GOALS: The aim of this study is to investigate whether there were any association between the 102 T/C and -1438 G/A polymorphisms of the 5-HT2A receptor gene and IBS, and abdominal pain, anxiety and depression. BACKGROUND: Genes involved in serotonin (5-HT) metabolism are good candidates for the pathogenesis of irritable bowel syndrome (IBS). Recently, a silent polymorphism in the 5-HT2A receptor gene was identified that is defined by a T to C transition at position 102. Also, a novel G to A base change at position -1438 of the promoter region has been detected in 5-HT2A receptor gene. STUDY: Fifty-four patients with IBS diagnosed according to the Rome 1 criteria and 107 healthy individuals were included in the study. PCR was used to amplify a 468-bp (G-->A) and 342-bp (T-->C) fragment of genomic DNA containing the polymorphism. Hospital anxiety and depression scale was used to assess the risk of depression and anxiety. Severity of chronic abdominal pain was determined by visual analogue scale (VAS). RESULTS: It was shown that there was a high incidence of homozygote C allele of the 102T/C polymorphism (%22.2; OR: 7.89, P = 0.04) and homozygote A allele of the -1438 G/A promoter region (%%37; OR: 11.14, P = 0.01) in patients with IBS. The risk of having an anxiety disorder was 83.3% in patients with C/C genotype, which was higher than other allele carrying patients, and overall mean (%52.7). (chi = 8.56, P = 0.014). The patients with T/T genotype had a VAS score of 54.93 +/- 2.59 mm, which was significantly higher than that of the patients with other genotypes (p1 = 0.02, p2 = 0.001). CONCLUSION: This study suggests that the patients with homozygote C allele of the 102 T/C polymorphisms or homozygote A allele of the -1438 G/A polymorphism of the 5-HT2A receptor gene, have a high risk of IBS. On the other hand, T/T genotype of 102 T/C polymorphism may be associated with more severe pain in patient with IBS.

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

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.