The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

Fonseka, Trehani M.; Tiwari, Arun K.; Gonçalves, Vanessa F.; Lieberman, Jeffrey A.; Meltzer, Herbert Y.; Goldstein, Benjamin I.; Kennedy, James L.; Kennedy, Sidney H.; Müller, Daniel J.

doi:10.3109/15622975.2014.984631

Cited by 28 publications

(22 citation statements)

References 210 publications

(184 reference statements)

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“…These variants are located in the ANKK1, DRD2 and DRD3 genes, respectively, which have already been addressed by other authors in the literature, relating them to the response to antipsychotics and metabolic alterations of the individuals making use of this drug treatment 4 - 5 . However, further in-depth analyses of how these variants in the DNA sequence can influence metabolic alterations in the carriers of these polymorphisms are necessary, as this theme is still little elucidated 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Although there is no single, globally accepted consensus, refractory schizophrenia can be characterized by partial response, for at least five years, to three different types of antipsychotics (at least two with different chemical structures); intolerance to adverse effects; and relapses or symptomatic deterioration despite the use of appropriate doses of the drugs 3 - 4 . The atypical antipsychotic clozapine is considered the gold standard for the drug treatment of refractory schizophrenia, being associated with clinical improvement and decreased hospitalizations 4 - 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Some SNPs alter the amino acid composition of the protein and the expression of the receptor, which may have an effect on the phenotype of an individual, and can also serve as molecular markers of predisposition to certain types of diseases. The ability to detect polymorphisms at the DNA level is the basis of several studies that aim to identify whether this variation causes or contributes to a specific phenotype 5 - 6 .…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

Pinto¹,

Freitas

Nunes

et al. 2018

Rev. Latino-Am. Enfermagem

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Objective:to estimate the prevalence of TaqIA, -141C and rs6280 polymorphisms of the ANKK1, DRD2 and DRD3 genes and evaluate their association with the occurrence of metabolic syndrome in patients with refractory schizophrenia. Method:cross-sectional study conducted in the Extended Western Region of Minas Gerais, with refractory schizophrenic patients using the antipsychotic clozapine. Sociodemographic, clinical, anthropometric, biochemical and genetic data were collected. Univariate analysis of the data was performed. Results:seventy-two patients participated in the study and the occurrence of Metabolic Syndrome was observed in 47.2% of them. There was no association between Metabolic Syndrome and the studied polymorphisms. There was a statistically significant difference in the low HDL parameter with homozygous genotype for the C allele of the -141C polymorphism of the DRD2 gene. Conclusion:a high prevalence of MS was evidenced. The -141C polymorphism was associated with low HDL. Genetic analysis and identification of metabolic alterations in this group of patients can guide drug treatment and provide a better quality of life.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

Pinto¹,

Freitas

Nunes

et al. 2018

Rev. Latino-Am. Enfermagem

View full text Add to dashboard Cite

show abstract

“…We found that variant sites across the IL-1β gene, specifically rs16944*GA, rs1143634*G, and rs4849127*A, were associated with greater AIWG in schizophrenia patients [161]. Our analyses further identified epistatic effects between IL-1β (rs13032029, rs16944) and the anorexigenic neurotrophin, brain-derived neurotrophic factor (BDNF), specifically the Val66Met variant, in predicting AIWG outcomes.…”

Section: Disruption Of Cytokine Signalling In Normal Weight Regulatiomentioning

confidence: 76%

“…Our analyses further identified epistatic effects between IL-1β (rs13032029, rs16944) and the anorexigenic neurotrophin, brain-derived neurotrophic factor (BDNF), specifically the Val66Met variant, in predicting AIWG outcomes. Epistatic interactions were also demonstrated between IL-6 rs2069837 and BDNF Val66Met [161]. Furthermore, an expansion of GWAS results from the Genetic Investigation of ANthropometric Traits (GIANT) identified associations between BMI and variants across genes associated with the MAPK pathway, which has been implicated in cytokine signalling [162].…”

Section: Disruption Of Cytokine Signalling In Normal Weight Regulatiomentioning

confidence: 99%

Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

Fonseka¹,

Müller

Kennedy

2016

Complex Psychiatry

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Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation. Since inflammatory cytokines are normally involved in anorexigenic responses, reduced inflammation has been independently shown to mediate changes in feeding behaviours and other metabolic parameters, resulting in obesity. Genetic variation in pro-inflammatory cytokines is also associated with both general obesity and weight change during AP treatment, and thus, may be implicated in the pharmacogenetics of AIWG. At this time, preliminary data support a cytokine-mediated model of AIWG which may have clinical utility in developing more effective metabolic monitoring guidelines and prevention measures. However, further research is still needed to clearly elucidate the validity of this immune model. This article reviews the evidence implicating inflammatory cytokines in AIWG and its potential clinical relevance.

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Genetics of IL6 polymorphisms: Case–control study of the risk of endometrial cancer

Cai¹,

Cui

Niu

et al. 2019

Molec Gen & Gen Med

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Background Endometrial cancer is the most common gynaecological malignancy. Cytokines gene may be important in endometrial cancer development. This study sought to investigate whether the IL4, IL6 two gene genetic variants were associated with susceptibility to endometrial cancer (EC) in Hainan Chinese Han women by a hospital‐based study. Methods The genetic polymorphisms for IL4 and IL6 were analyzed by Agena MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. Results We observed a significant increase in risk of endometrial cancer of rs1524107 (IL6) (T/C, OR = 1.61, 95% CI = 1.09–2.37, p = 1.55 × 10−2), rs2066992 (IL 6) (OR = 3.09, 95% CI = 2.11–4.53, p = 3.13 × 10−9). However, for IL4 gene, no associations emerged the SNP and EC risk. Conclusion This study demonstrated that IL6 gene polymorphisms are significantly associated with increased EC susceptibility in Hainan Chinese Han women.

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The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

Abstract: Background: Antipsychotics with high weight-inducing propensities influence the expression of immune

Cited by 28 publications

References 210 publications

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

Genetics of IL6 polymorphisms: Case–control study of the risk of endometrial cancer

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