CT genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is protector factor of major depressive disorder in the Tunisian population: a case control study.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis. The aim of this research is to study the association between the C677T polymorphism of MTHFR gene and depression in Tunisian population, to explore their relationship with clinical and therapeutic characteristics of this disease. And it may lead to discover a novel marker to identify a patient with a higher risk of development of depressive disorder to be. This marker can be used for better therapeutic management and prevent disease installation. METHODS: Our study included 208 depressive patients, 187 controls aged between 44.1 ± 13.5 and 38.9 ± 13.2 years, respectively. MTHFR gene polymorphisms were determined by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). RESULTS: No significant difference was detected in the distribution of the genotype frequencies of MTHFR C677T polymorphisms (χ (2) = 5.443, df = 2, p = 0.066) between patients and controls. But when we study the risk of these genotypes, CT genotype is significantly more frequent in controls compared to patients, it may be a protection from depression (OR = 0.655, CI 95 % = 0.432-0.995, p = 0.047, OR* = 0.638, CI 95 %* = 0.415-0.983, p* = 0.04, before and after adjustment). Women, TT Genotype can increase four times the risk to be depressive. Addictive behavior seems to be associated with CT genotype and there was no significant association between clinical and therapeutic characteristics and this polymorphism. CONCLUSION: This paper is the first study to prove that CT genotype of MTHFR C677T polymorphism may protect from depression and TT genotype seems to be associated with women's depression. Further studies are required with other polymorphisms and biochemical factors that must be investigated to clarify the implication of MTHFR C677T polymorphism in the pathophysiology of depression.

[Pseudocholinesterase activity in type 1 bipolar patients]. / Étude de l'activité pseudocholinestérasique chez des patients bipolaires de type 1.

This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 ±â€Š12.2 and 36.4 ±â€Š15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plus™. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk.

[Risk of hyperthyroidism in a Tunisian population of smokers]. / Risque d'hyperthyroïdie dans une population de fumeurs tunisiens.

OBJECTIVES: This study aimed to examine the effect of cigarette smoking on thyroid function especially TSH and FT4 levels and to determine the correlation between these parameters and the biological tobacco markers: plasma thiocyanate and cotininuria. METHODS: The initial study was conducted on 300 voluntary subjects, 162 current smokers, 27 former smokers and 111 nonsmokers aged respectively 35.4±16.1, 31.6±1.8 and 38.0±14.6 years. TSH and FT4 levels were determined using electrochemiluminescence, cotinine by homogenous enzymes immunoassay and thiocyanate by selective electrode. RESULTS: Before and after adjustment for potentials confounder factors, we found a significant decrease of TSH and a significant increase of FT4 levels according to smoking status. In current and former smokers, we found significant decrease in TSH and increase in FT4 levels compared to nonsmokers. Moreover, we noted a significant decrease of TSH levels in subjects smoking more than 40 cigarettes/day compared to those smoking less than 20 cigarettes/day. Additionally, TSH levels were significantly reduced in subjects smoking more than 5 years compared to those who smoked < 5 years. In smokers, cotininuria and plasma thiocyanates presented a negative correlation with TSH and a positive correlation with FT4 levels. CONCLUSION: cigarette smoking is associated to perturbations in FT4 and TSH levels, these perturbations were strongly correlated with smoking status parameters. The associations with smoking cessation suggest that smoking may have reversible effects on thyroid function. Therefore, it is recommended to stop or reduce smoking and to introduce testing of thyroid estimation as a routine test, especially in subjects at risk.

Effect of cigarette smoking on paraoxonase 1 activity according to PON1 L55M and PON1 Q192R gene polymorphisms.

OBJECTIVE: This study aims to investigate the effect of cigarette smoking on paraoxonase 1 (PON1) activity according to PON1 L55M and PON1 Q192R gene polymorphisms. MATERIALS AND METHODS: Our sample included 300 voluntary subjects: 138 nonsmokers and 162 current smokers aged 38.47 ± 21.91 and 35.55 ± 16.03 years, respectively. PON1 activity was determined by kinetic methods. L55M and Q192R gene polymorphisms of PON1 were determined by multiplex polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: We found in smokers a significant decrease of PON1 activity before and after adjustment. We noted a significant association between smoking status and lower PON1 activity [odds ratio (OR) = 3.03, confidence interval 95% = 1.5-5.9, p = 0.001]. In smokers, there was significant association between PON1 activity and PON1 L55M polymorphisms (p = 0.01). Also, the 55MM genotype presented the lowest paraoxonase activity, while the 55LL genotype showed the highest one. After adjustment for confounding variables, smokers with PON1 L55M polymorphism had the highest risk for lower PON1 activity; however, PON1 Q192R genotype might protect smokers from decrease in PON1 activity. We found significant interaction between the effect of cigarette smoking and both PON1 L55M and PON1 Q192R polymorphisms on lower PON1 activity. CONCLUSIONS: Cigarette smoking was significantly associated with decrease in PON1 activity. Moreover, PON1 L55M polymorphism predisposes smokers to decreased PON1 activity in contrast to PON1 Q192R genotype.

Effect of cigarette smoking on plasma homocysteine concentrations.

BACKGROUND: Cigarette smoking has been recognized as a major risk factor for cardiovascular disease, while the role of homocysteine is still not clear. This study investigated the effects of smoking on plasma homocysteine concentration and determined the correlation between this parameter and biological markers of tobacco use, such as plasma thiocyanate and urine cotinine. METHODS: Folate, vitamin B12 and homocysteine were measured in 300 subjects: 138 non-smokers and 162 smokers using immunoassay methods. Cotinine was measured using an enzymatic colorimetric method and thiocyanate by a selective electrode. RESULTS: In smokers, we found a significant increase in homocysteine and a decrease in folate and vitamin B12 levels compared to non-smokers. Homocysteine was strongly correlated with the duration of use and the number of cigarettes consumed. Folate and vitamin B12 were significantly reduced in subjects smoking for more than 20 years compared to those who smoked less than 5 years. Among smokers, we noted a positive correlation between homocysteine and both plasma thiocyanates and cotininuria, and a negative-correlation between cotininuria and plasma folate. CONCLUSIONS: Cigarette smoking increases homocysteine, which is strongly correlated with cotininuria and plasma thiocyanates. Moreover, smokers had tendency to develop hypofolatemia and hypovitamin B12, particularly when the duration of consumption exceeded 20 years.

Hyperhomocysteinemia in Tunisian bipolar I patients.

AIMS: The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P < 0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P < 0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92-15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was >12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine. CONCLUSION: Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.

Effect of cigarette smoking on plasma uric acid concentrations.

OBJECTIVES: The purpose of this study was to examine the effect of cigarette smoking on plasma uric acid concentration and to determine the correlation between this parameter and the biological tobacco markers, plasma thiocyanate and urinary cotinine. METHODS: The initial study was conducted on 300 subjects; 138 of them were nonsmokers (62 men and 76 women) aged 14-72 years and 162 were current smokers (145 men and 17 women) aged 16-85 years. Uric acid, creatinine, and urinary cotinine were determined by the enzymatic colorimetric method and plasma thiocyanate by selective electrode. RESULTS: Plasma uric acid concentration was significantly lower in smokers than in nonsmokers. A statistically significant negative correlation was noted between the smoking status parameters, including both the number of cigarettes smoked/day (F (3-161) = 12.063; r = -0.9968; p = 0.0001) and the duration of smoking (F (3-161) = 1.305; r = -0.9406; p = 0.0274), and the plasma uric acid. Among smokers, we noted a negative correlation between uric acid and both plasma thiocyanates (r = -0.437; p < 0.05) and urinary cotinine (r = -0.580; p < 0.05). CONCLUSION: After excluding the other factors affecting the uric acid levels, the significant low plasma uric acid in smokers was attributed to a reduction of the endogenous production as a result of the chronic exposure to cigarette smoke that is a significant source of oxidative stress. Therefore, it is recommended to stop or reduce smoking and to introduce plasma uric acid estimation as a routine test, since it is cheap and simple to reflect the antioxidant level.

Lower paraoxonase 1 activity in Tunisian bipolar I patients.

BACKGROUND: The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. PATIENTS AND METHODS: Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific). RESULTS: Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels. CONCLUSIONS: Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

[Paraoxonase 1 (PON1) activity and lipid parameters in Tunisian smokers]. / Etude de l'activité de la paraoxonase 1 (PON1) et du profil lipidique dans une population de fumeurs tunisiens.

This study aims at examine the effect of cigarettes smoking on paraoxonase 1 (PON1) activity and lipid profile. Our study included 102 smokers aged 35.5 +/- 16.0 years and 98 non-smokers aged 38.5 +/- 21.9 years. Total cholesterol (TC), triacylglycerols (TG), HDL cholesterol (CHDL) and LDL-cholesterol (cLDL) were determined by enzymatic colorimetric methods. ApoA1 and ApoB and Lp(a) were analyzed by immunoturbidimetry on Konélab 30, PON1 activity was measured by a kinetic method. Plasma CT, TG, cLDL, Lp(a) and ApoB/ApoA1 ratio appeared significantly higher in the smokers when compared to nonsmokers, since cHDL levels were lower. In addition, TG values were significantly higher in subjects smoking more than 30 cigarettes/day as compared to those smoking 5-10 cigarettes/day. We noted a significant decrease of PON1 activity in smokers compared to non smokers (94 +/- 104 vs 158 +/- 133 IU/L), with regression of PON1 activity according number of cigarettes/day. In conclusion, hypertriglyceridemia, low levels of cHDL, high levels of ApoB/ApoA1 and significant decrease of PON1 activity confirm the high risk of cardiovascular diseases in smokers.

[Obesity and dyslipidemia in Tunisian bipolar subjects]. / Obésité et dyslipidémie chez des patients bipolaires tunisiens.

This study aims to investigate the prevalence of obesity and overweight and their association with lipid parameters in bipolar patients. Our study included 130 patients with bipolar disorder and 130 control subjects aged respectively 37.9 +/- 12.1 and 37.2 +/- 13.1 years. Obesity was evaluated by body mass index (BMI). Concentrations of total cholesterol, triglycerides, cLDL and cHDL were determined by enzymatic methods and ApoA1, ApoB and Lp(a) by techniques immunoturbidimetric. The prevalence of obesity in patients is 30.1% vs 12.3% in controls. A significant increase in BMI was noted in patients compared with controls regardless of sex and tobacco status and in patients aged less than 35 years and those consumers of alcohol. The majority of obese and overweight patients are treated with valproic acid. We found increase in cholesterol (4.41 +/- 1.02 vs 3.90 +/- 0.98 mmol/L), in cLDL (2.13 +/- 1.09 vs 1.29 +/- 0.56 mmol/L) and in Lp(a) (236 +/- 207 vs 163 +/- 150 mg/L) and decrease in HDLc (0.98 +/- 0.28 vs 1.09 +/- 0.36 mmol/L), more frequent at the obese patients and those presenting an overweight. In conclusion, in bipolar patients, obesity and overweight are frequent and associated with perturbations in lipid profile particularly an increase in total cholesterol, cLDL and Lp(a) and decrease in cHDL that increase the risk of cardiovascular disease.

Association between bipolar I disorder and the L55M and Q192R polymorphisms of the paraoxonase 1 (PON1) gene.

BACKGROUND: The purpose of this work was to study the association between the PON1 L55M and Q192R polymorphisms and bipolar I disorder in Tunisian patients and to explore their relation to the sociodemographic, clinical and therapeutic characteristics of this disease. PATIENTS AND METHODS: Our study included 109 patients with bipolar I disorder and 110 controls aged 39.4±11.8 and 37.3±9.2 years, respectively. L55M and Q192R of the PON1 gene polymorphisms were determined by multiplex polymerase chain reaction. RESULTS: Significant difference was detected in the distribution of the genotype frequencies of L55M and Q192R polymorphisms (χ²=6.32, df=2, p=0.04; χ²=10.15, df=2, p=0.006 respectively) between patients and controls. We noted significant association between bipolar I disorder and QR and RR genotypes (OR 2.06, CI 95% 1.10-3.84, p=0.02; OR 1.72, CI 95% 1.07-2.75, p=0.02 respectively) and between this disease and LM and MM genotypes (OR 2.22, CI 95% 1.19-4.15, p=0.012; OR 3.04, CI 95% 1.60-5.77, p=0.01 respectively). There were no significant differences in gender, age at onset, illness episode and treatment among all genotypes. However, Q192R polymorphism was significantly associated with age and patients with RR genotype were the youngest. CONCLUSION: Bipolar I disorder was significantly associated with L55M and Q192R polymorphisms, suggesting that these polymorphisms may play a role for development of bipolar I disorder. There was no significant association between the clinical and therapeutic characteristics of this population and these polymorphisms. Further studies are required to clarify the implication of these polymorphisms in the pathophysiology of bipolar I disorder.

Interference of tobacco smoke with immunochromatography assay for urinary drug detection.

BACKGROUND: This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection. METHODS: Our study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN(-)) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay. RESULTS: False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ(2) = 116.62, p < 10(-3)). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 µg/µmol; p < 10(-3)) and for plasma SCN(-) (101.6 ± 3.4 Vs 98.8 ± 2.1 µmol/L; p = 10(-3)). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 µg/µmol and 10.5 years were found as predictive factors of false positive results. CONCLUSION: Tobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.

Thyroid function and lipid profile in bipolar I patients.

OBJECTIVE: This study aims to evaluate the prevalence of thyroid dysfunctions and to explore their association with perturbations in lipid profile in bipolar I patients. PATIENTS AND METHODS: Our study included 130 bipolar I patients diagnosed according to the DSM IV, and 124 control subjects aged respectively 37.9±12.1 and 37.6±13.2 years. TSH and FT4 were determined using electrochemiluminescence. Total cholesterol, triglycerides, c-LDL and c-HDL were determined by enzymatic colorimetric methods and ApoA1, ApoB and Lp(a) by immunoturbidimetric techniques on Konélab 30™. RESULTS: Patients had significantly higher TSH values than controls and had perturbations in lipid profile. 0.7% and 28.5% of patients had respectively hyperthyroidism and hypothyroidism. Hypothyroidism was associated with obesity and perturbations in lipid profile particularly increase in total cholesterol, c-LDL, ApoB, ApoB/ApoA1 and Lp(a) and decrease in ApoA1 and c-HDL. Moreover, it was associated with lithium and valproic acid treatment. CONCLUSIONS: Hypothyroidism was frequent in bipolar patients. It was significantly associated with obesity and perturbations in lipid profile. Therefore, bipolar patients require specific care, particularly for thyroid, lipid profile and weight; the effectiveness of this care will be evaluated during follow-up period.