A Descriptive Study

The synapsins: Key actors of synapse function and plasticity

Effects of drugs on clinical laboratory tests

Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined “adipocytokines,” protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs (“adiponectin system”), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases.

/pdf/new-insight-into-adiponectin-role-in-obesity-and-obesity-3vpt3r2uoo.pdf

New insight into adiponectin role in obesity and obesity-related diseases.

Background There is considerable interest in the use of next-generation sequencing to help diagnose unidentified genetic conditions, but it is difficult to predict the success rate in a clinical setting that includes patients with a broad range of phenotypic presentations.

Methods The authors present a pilot programme of whole-exome sequencing on 12 patients with unexplained and apparent genetic conditions, along with their unaffected parents. Unlike many previous studies, the authors did not seek patients with similar phenotypes, but rather enrolled any undiagnosed proband with an apparent genetic condition when predetermined criteria were met.

Results This undertaking resulted in a likely genetic diagnosis in 6 of the 12 probands, including the identification of apparently causal mutations in four genes known to cause Mendelian disease ( TCF4, EFTUD2, SCN2A and SMAD4 ) and one gene related to known Mendelian disease genes ( NGLY1 ). Of particular interest is that at the time of this study, EFTUD2 was not yet known as a Mendelian disease gene but was nominated as a likely cause based on the observation of de novo mutations in two unrelated probands. In a seventh case with multiple disparate clinical features, the authors were able to identify homozygous mutations in EFEMP1 as a likely cause for macular degeneration (though likely not for other features).

Conclusions This study provides evidence that next-generation sequencing can have high success rates in a clinical setting, but also highlights key challenges. It further suggests that the presentation of known Mendelian conditions may be considerably broader than currently recognised.

https://jmg.bmj.com/content/jmedgenet/49/6/353.full.pdf

Clinical application of exome sequencing in undiagnosed genetic conditions

The coronavirus disease 2019 (COVID-19) crisis has greatly affected human lives across the world. Uncertainty and quarantine have been affecting people’s mental health. Estimations of mental health problems are needed immediately for the better planning and management of these concerns at a global level. A rapid scoping review was conducted to get the estimation of mental health problems in the COVID-19 pandemic during the first 7 months. Peer-reviewed, data-based journal articles published in the English language were searched in the PubMed, Medline, and Google Scholar electronic databases from December 2019 to June 2020. Papers that met the inclusion criteria were analyzed and discussed in this review. A total of 16 studies were included. Eleven studies were from China, two from India, and one from Spain, Italy, and Iran. Prevalence of all forms of depression was 20%, anxiety 35%, and stress 53% in the combined study population of 113,285 individuals. The prevalence rate of all forms of depression, anxiety, stress, sleep problems, and psychological distress in general population was found to be higher during COVID-19 pandemic.

/pdf/prevalence-of-depression-anxiety-and-stress-during-covid-19-1ojl9sxn6g.pdf

Prevalence of Depression, Anxiety, and Stress during COVID-19 Pandemic

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT



• The SCN1A and SCN2A genes encode α subunits of the neuronal voltage-gated sodium channel, which are targets for various antiepileptic drugs such as carbamazepine, phenytoin, valproate and others.



• Recent studies have demonstrated that various genetic variants of these channel genes play important role in the pathogenesis and therapy of epilepsy.



WHAT THIS STUDY ADDS



• This study demonstrates a significant association between the SCN1A c.3184 AG; AG genotype and epilepsy.



• However SCN2A c.56 GA; allele ‘A’ was significantly associated with multiple drug resistance in epilepsy in north Indian population.



AIMS

To evaluate sodium channel genes as candidates for epilepsy susceptibility and their role in therapeutic efficacy, we screened coding single-nucleotide polymorphism of SCN1A p. Thr 1067 Ala or c.3184 AG (rs2298771) and SCN2A p.Arg19Lys or c.56 GA (rs17183814) in north Indian epilepsy patients.



METHODS

The genotyping was performed in 160 control subjects and 336 patients with epilepsy, of whom 117 were drug resistant and 219 were drug responsive. Therapeutic drug monitoring for phenytoin, carbamazepine, phenobarbital and valproate was also performed in 20% of the patients to confirm compliance.



RESULTS

AG genotype of SCN1A 3184 AG polymorphism was significantly higher and associated in epilepsy patients [P= 0.005; odds ratio (OR) 1.76, 95% confidence interval (CI) 1.19, 2.61], whereas A variant of SCN2A c.56 GA was associated with multiple drug resistance in north Indian patients with epilepsy (P= 0.03; OR 1.62, 95% CI 1.03, 2.56).



CONCLUSIONS

Overall, results indicate a differential role of genetic polymorphisms of sodium channels SCN1A and SCN2A in epilepsy susceptibility and drug response.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2009.03437.x

Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population.

No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population.

Background: In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways. Materials and Methods: In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resistant epilepsy and 274 patients were diagnosed as having drug-responsive epilepsy. We selected a total of 10 candidate gene polymorphisms belonging to three major classes, namely drug transporters, drug metabolizers and drug targets. These genetic polymorphism included CYP2C9 c.430C>T (*2 variant), CYP2C9 c.1075 A>C (*3 variant), ABCB1 c.3435C>T, ABCB1 c.1236C>T, ABCB1 c.2677G>T/A, SCN1A c.3184 A> G, SCN2A c.56G>A (p.R19K), GABRA1c.IVS11 + 15 A>G and GABRG2 c.588C>T. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, and each genotype was confirmed via direct DNA sequencing. The relationship between various genetic polymorphisms and responsiveness was examined using binary logistic regression by SPSS statistical analysis software. Results: CYP2C9 c.1075 A>C polymorphism showed a marginal significant difference between drug resistance and drug-responsive patients for the AC genotype (Odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.32-1.00; P = 0.05). In drug transporter, ABCB1 c.2677G>T/A polymorphism, allele A was associated with drug-resistant phenotype in epilepsy patients ( P = 0.03, OR = 0.31, 95% CI = 0.10-0.93). Similarly, the variant allele frequency of SCN2A c.56 G>A single nucleotide polymorphism was significantly higher in drug-resistant patients ( P = 0.03; OR = 1.62, 95% CI = 1.03, 2.56). We also observed a significant difference at the genotype as well as allele frequencies of GABRA1c.IVS11 + 15 A > G polymorphism in drug-resistant patients for homozygous GG genotype ( P = 0.03, OR = 1.84, 95% CI = 1.05-3.23) and G allele ( P = 0.02, OR = 1.43, 95% CI = 1.05-1.95). Conclusions: Our results showed that pharmacogenetic variants have important roles in epilepsy at different levels. It may be noted that multi-factorial diseases like epilepsy are also regulated by various other factors that may also be considered in the future.

Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population

A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case-control study. Hormone and glucose levels were estimated using standard protocols. Genotyping of UCP-2 gene polymorphism for all subjects was performed by the PCR-RFLP polymerase chain reaction (PCR) method. Higher Systolic blood pressure, Diastolic blood pressure, Waist to hip ratio, Leptin, Insulin, and blood glucose levels were observed in obese than non-obese (P < 0.05). The distributions of genotype (0.001) and allele (0.003) were significantly different between the non-obese and the obese groups. In the obese group, subjects with the A allele showed significant high insulin levels (<0.001) in comparison with A allele non-carriers. In conclusion, our results suggest that the -866 AA genotype and A allele of the UCP2 gene is associated with obesity and A allele associated with hyperinsulinemia in obese subjects.

Ram Lakhan

Papers

Prevalence of Depression, Anxiety, and Stress during COVID-19 Pandemic

Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population.

No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population.

Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population

A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians.