Association of TLR-4 896A/G, TLR-4 1196C/T, and TLR-9 C/T polymorphism with schizophrenia in Indian Bengalee patient.

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, = 0.01) and A/G genotype of TLR-4 rs4986790 ( = 0.04), T allele (OR = 4.09, = 0.01) and C/T genotype of TLR-4 rs4986791 ( = 0.05), and T allele of TLR-9 rs352140 (OR = 1.77; = 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, = 0.01) and TLR-9 rs352140 (OR = 2.88, = 0.005).

CONCLUSION

The findings suggest that SNPs in TLR genes rs4986790, rs4986791, and rs352140 may confer susceptibility to schizophrenia among Indian Bengalee patients.