Lack of Association between the IL6R Gene Asp358Ala Variant (rs2228145), IL-6 Plasma Levels, and Treatment Resistance in Chilean Schizophrenic Patients Treated with Clozapine

Abstract

Alterations in neuroinflammatory processes have been suggested to contribute to the development of Schizophrenia (SZ); one component of the inflammatory system that has been linked to this disorder is interleukin-6 (IL-6). The minor allele of rs2228145, a functional polymorphism in the IL-6 receptor gene, has been associated to elevated IL-6 plasma levels and increased inflammatory activity, making it an interesting candidate to study as a possible factor underlying clinical heterogeneity in SZ. We studied a sample of 100 patients undergoing treatment with clozapine. Their symptoms were quantified by Brief Psychotic Rating Scale; those with the lowest scores (“remitted”) were compared with the highest (“clozapine treatment resistant”). We determined allelic frequencies for rs2228145 and IL-6 plasma levels. Our results do not support a role of IL-6 in response to treatment with clozapine. Further studies accounting for potential confounding factors are necessary.

Polymorphisms in Schizophrenia-Related Genes Are Potential Predictors of Antipsychotic Treatment Resistance and Refractoriness

“…We found no differences in genotype or allele frequency between patients who remitted with clozapine and those with persistent symptoms. Furthermore, we found no difference in the median interleukin-6 plasma level by genotype ( Cavieres et al, 2019 ). For the present study, we compared the full spectrum of treatment responses, from responsive to refractory.…”

High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case–Control Study

“…Third, we analyzed the association between the rs2228145 polymorphism of the IL6R gene and individuals with suicide attempts, for the minor allele of the rs2228145 polymorphism (Ala) has been associated with elevated IL-6 levels in the serum and circulating/plasma levels in individuals with schizophrenia [ 48 ]. Then, we considered it important to evaluate the genotypic distribution of the IL6R gene in suicide attempts.…”