Association Of Snp8nrg241930 Polymorphism in The Neuregulin 1 (Nrg1) Gene with Schizophrenia Susceptibility and Clinical Symptom Improvement Following Risperidone Treatment

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Andi Nurul Khadijah, Saidah Syamsuddin, Kristian Liaury, Irfan Idris, Rusdina Bte Ladju, Erlyn Limoa, Sonny Teddy Lisal

Abstract

Evidence linking neuregulin 1 (NRG1) polymorphisms with schizophrenia susceptibility and antipsychotic response remains inconsistent. This analytical observational study combined a case–control genetic analysis with prospective longitudinal assessment to evaluate SNP8NRG241930 (NRG1 rs62510682) in relation to schizophrenia and symptom changes during risperidone treatment. A total of 200 participants were included: 100 patients with schizophrenia and 100 healthy controls. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism. Patients with schizophrenia were followed for 8 weeks during risperidone treatment, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline, week 4, and week 8. Genotype distribution differed significantly between groups (Fisher–Freeman–Halton exact P=0.013), whereas allele frequencies did not (P=0.313); the T allele was not significantly associated with schizophrenia (OR 1.23, 95% CI 0.83–1.82). The control group deviated significantly from Hardy–Weinberg equilibrium (P<0.001). Generalized estimating equation analysis showed significant improvement over time in all PANSS domains (all P<0.001), but no significant time-by-genotype interactions were observed. SNP8NRG241930 showed a case–control difference in genotype distribution but was not associated with differential symptom trajectories during risperidone treatment. The Hardy–Weinberg disequilibrium in controls warrants cautious interpretation of the susceptibility finding.

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