DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022) were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023) and allele (P = 0.0063) increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia.

Study demonstrates that antipsychotic drugs can influence host methylome and thereby indicating its role in mediating a strong pharmacoepigenomic response.

Prior infection with adenovirus 36 (Adv36) has been associated with increased adiposity, improved insulin sensitivity, and a lower prevalence of diabetes. This study investigated the prevalence of Adv36 seropositivity and its association with obesity and diabetes among adults attending a diabetes centre in the UAE.Participants (N = 973) with different weight and glucose tolerance categories were recruited. Adv36 seropositivity (Adv36 + ) was assessed using ELISA. Differences among groups were analyzed using statistical tests as appropriate to the data. Prevalence of Adv36+ in the study population was 47%, with no significant difference in obese and non-obese subgroups (42.5% vs 49.6% respectively; p=non-significant). Females were more likely to be Adv36+ compared to males (odds ratio 1.78; 95% CI 1.36–2.32, p < 0.001). We found no significant association between Adv36 seropositivity and different BMI categories, or glucose tolerance status. In our population, the effect of Adv36 infection on lipid profile varied between healthy individuals and individuals with obesity. Adv36 infection is more prevalent in the UAE than in other countries but has no association with obesity. Our study found that females were more likely to be Adv36 positive regardless of weight or diabetes status.

The study demonstrates that antipsychotic drugs can influence miRNA-mediated epigenetic response in pharmacogenes resulting in modulating therapeutic response.

Homocysteine (Hcy) is known to be a prognostic marker for neurological, cardiovascular and cerebrovascular diseases and several other pathophysiological conditions. A sudden surge in Hcy can increase cardiovascular events. Hemodynamic modulations are known to be associated with individual's chronotype. Therefore, precise monitoring of Hcy is crucial for evaluating its impact on risk. The aim of the present study was to investigate the rhythmicity of Hcy under controlled dietary conditions and whether this rhythmicity is under the genetic control of circadian rhythm. Five subjects were selected from 200 Malayalam speaking healthy ethnic individuals who were screened for functionally critical variants of MTHFR and hCLOCK genes. MTHFR is the rate-limiting enzyme in the methionine cycle and critical for regulating Hcy levels while hCLOCK is a critical gene responsible in regulating the day and night cycles. Rhythmicity in Hcy levels were observed in all the subjects with a consensus on a morning nadir and an evening peak. Gender specific stratification of Hcy levels were observed among similar genotypes of MTHFR and hCLOCK genes. Variations from the conventional rhythmicity of Hcy were observed among similar genotypes of MTHFR and dissimilar hCLOCK genotypes. A reduced plasma Hcy in hCLOCK rs1801260 CC genotype individuals were observed in contrast to CT genotype individuals. The study tends to suggest that Hcy and body time are genetically interdependent and throws light on some of the previously unexplained reasons for variability in Hcy levels. A population specific variation of MTHFR and hCLOCK genes also highlights ethnicity specific risk management.