A search was undertaken in the most eastern part of the Himalayan kingdom of Bhutan for the plants which are causing severe losses of yaks due to pyrrolizidine alkaloid poisoning. Two Senecio and three Ligularia species were found on yak pastures at altitudes between 3000 and 4000 m, including one so far underscribed Ligularia species. None was previously known to contain pyrrolizidine alkaloids. Another Senecio species was found between 2500 and 3000 m, an altitude too low for yaks to be kept but significant for other cattle. The search was supported by field chemical tests for the alkaloids and the diagnosis was later confirmed by thin layer chromatography and high pressure liquid chromatography. Two of the Senecio species had exceptionally high concentrations of pyrrolizidine alkaloids of about 0.5 per cent in the dry matter.
Background:
Chronic low-grade inflammation triggered by viral agents is a suggested etiological factor for schizophrenia. However, the underlying mechanism of inflammation and genetic predisposition to schizophrenia is poorly understood. Toll-like receptor (TLR) is a potential candidate gene to understand the inflammatory process and genetic predisposition to schizophrenia as they are known to express widely in brain cells and can modulate cytokine synthesis through recognition of pathogen-associated molecular patterns. To date, no TLR mutations or single nucleotide polymorphisms have been established as accepted risk factors for schizophrenia.
Aim:
Therefore, the present investigation was undertaken to study the role of single nucleotide polymorphisms (SNPs) within the TLR genes in the etiopathology of schizophrenia.
Methods:
A total of 120 India-born Bengalee schizophrenia patients fulfilling diagnostic and statistical manual of mental disorders-V criteria, and 145 age, sex, and ethnicity-matched healthy controls were included in the study. Previous virally associated SNPs in TLR genes were genotyped by Polymerase chain reaction-restriction fragment length polymorphism assay. The allele frequency was compared using the odds ratio, and the association was studied under five inheritance models using the SNPStats program.
Results:
The frequencies of G allele (OR = 2.68, P = 0.01) and A/G genotype of TLR-4 rs4986790 (P = 0.04), T allele (OR = 4.09, P = 0.01) and C/T genotype of TLR-4 rs4986791 (P = 0.05), and T allele of TLR-9 rs352140 (OR = 1.77; P = 0.00) were found to be significantly high in patients. The dominant model was the optimum genetic model for TLR-4 rs4986790 (OR = 3.24, P = 0.01) and TLR-9 rs352140 (OR = 2.88, P = 0.005).
Conclusion:
The findings suggest that SNPs in TLR genes rs4986790, rs4986791, and rs352140 may confer susceptibility to schizophrenia among Indian Bengalee patients.
The results provide the evidence for a possible immunomodulatory effect of antipsychotic drugs on CRP. Future investigations including the study of antipsychotics separately may help to understand the differential effects of individual antipsychotics on CRP level. Additional studies with a larger sample size of psychotropic medication-free patients may help to verify the role of inflammation in schizophrenia patients of this region.
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