MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Acute Reversible Motor Predominant Polyradiculoneuropathy among Thai Prisoners after the Outbreak of H3N2 Influenza: A Case Series

Objective: This study aims to describe the clinical, laboratory and electrophysiological findings of the prisoners who developed acute reversible motor predominant polyradiculoneuropathy after the outbreak of H3N2 influenza. Material and Methods: Among H3N2 infected Thai prisoners, all patients with acute flaccid weakness were included in this retrospective case series. We analyzed the results of electromyography (EMG), cerebrospinal fluid analysis, and serum levels of antiganglioside antibodies, folate, thiamine, and vitamin B12.Results: Among 262 H3N2 influenza patients, motor predominant polyradiculoneuropathy predominantly affecting the lower limbs developed in 10 patients. EMG revealed significantly decreased compound muscle action potentials with preserved distal latencies and conduction velocities in the peroneal nerves. Early fibrillation potentials were demonstrated on EMG performed 12-14 days post-onset of symptoms. The cerebrospinal fluid study showed normal profiles. All laboratory results appeared normal except for the significantly low mean±standard deviation serum folate level of 1.80± 0.78 [reference value 3.89–26.80 nanograms per milliliter (ng/mL)] as compared to the mean serum folate level in the normal Thai population of 10.80 ng/mL (p-value<0.001, 95% confidential interval -9.55 to -8.45). All patients were treated with 15 milligram per day of folic acid and all patients improved clinically. Conclusion: Although the relationship between low plasma folate level and polyradiculoneuropathy is unclear, a superimposed folate deficiency contributing to the pathophysiology is possible.

Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and precancerous lesions

Background This study evaluated gene-nutrition interactions between folate and the aberrant DNA methylation of tumor suppressor genes in different stages of carcinogenesis of esophageal squamous cell carcinoma (ESCC). Methods Two hundred ESCC cases, 200 esophageal precancerous lesion (EPL) cases, and 200 controls matched by age (± 2 years) and gender were used for this study. Baseline data and dietary intake information was collected via questionnaire. The serum folate levels and methylation status of promoter regions of p16 and p53 were detected. Results The interactions of increased serum folate level with unmethylated p16 and p53 promoter regions were significantly associated with a reduced risk of both EPL and ESCC (p for interaction < 0.05). The interactions of the lowest quartile of serum folate level with p16 or p53 methylation was significantly associated with an increased risk of ESCC (OR = 2.96, 95% CI, 1.45–6.05; OR = 2.34, 95% CI, 1.15–4.75). An increased serum folate level was also related to a decreasing trend of EPL and ESCC risks when p16 or p53 methylation occurred. The interaction of spinach, Chinese cabbage, liver and bean intake with unmethylated p16 and p53 was significantly associated with a reduced risk of EPL or ESCC (p for interaction < 0.05). Conclusions The interactions between a high folate level and unmethylated p16 and p53 promoter regions may have a strong preventive effect on esophageal carcinogenesis. Additionally, a high folate level may offset the tumor-promoting effects of aberrant DNA methylation of the genes, but it is also noteworthy that a very high level of folate may not have a protective effect on EPL in some cases.

High Serum Folate Concentration Is Associated with Better Lung Function in Male Chronic Obstructive Pulmonary Disease Patients Who Are Current Smokers: Analysis of Nationwide Population-Based Survey

Folate, folic acid, has a role in mitigating inflammatory reactions in the human body. This study aimed to evaluate the association of serum folate levels with lung function in chronic obstructive pulmonary disease (COPD) patients. Of the 8149 participants of the 2016 Korean National Health and Nutrition Examination Survey (KNHANES), 311 subjects (192 males and 119 females) having COPD defined by the lower fifth percentile of the reference population were selected. Pearson’s correlation coefficient was used to investigate the relationship between serum folate level and lung function measurements. The association between the serum folate level and lung function in patients with COPD was evaluated using multivariable linear regression analysis after adjustment for age, sex, height, high sensitivity C-reactive protein, total calorie intake, residence, smoking status and smoking pack–years, education, and household income. The serum folate level showed a positive correlation with the predicted percentage of forced expiratory volume in one second (FEV1%). In males, a trend for a positive correlation with serum folate level was observed in predicted FEV1%, FEV1 value, predicted percentage of forced vital capacity (FVC%), FVC value, and peak expiratory flow (PEF). No significant correlation between the serum folate level and lung function in females was observed. In the multivariable linear regression model, the serum folate level was associated with an increase in predicted FEV1%, FEV1 value, predicted FVC%, FVC value, and PEF; however, the significance was only observed in males, especially among current smokers. High serum folate level was positively associated with lung function measurements in male COPD patients who were current smokers. Further longitudinal studies are needed to elucidate the underlying mechanisms.

Celiac disease with Budd–Chiari syndrome: A rare association

Budd–Chiari syndrome is characterized by hepatic venous outflow tract obstruction. We describe an 18-year-old female of known celiac disease presented with progressive abdomen distention and shortness of breath for the last 1 month. Computed tomography of abdomen revealed hepatic vein obstruction. The patient was diagnosed with Budd–Chiari syndrome. Coagulation profile showed an increased homocysteine level. Serum folate level was also decreased. The patient was put on oral anticoagulant with a gluten-free diet. After 4 weeks, the patient showed significant improvement with decreased ascites. The association of Budd–Chiari syndrome with Celiac disease has not yet been fully understood. There have been few reports that described this rare association. Budd–Chiari syndrome should be considered as an important differential in a patient with unexplained ascites and celiac disease.