Prolactin gene polymorphism (− 1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics

Svetlana A. Ivanova, Diana Z. Osmanova, Anastasia S. Boiko, Ivan V. Pozhidaev, Maxim B. Freidin, Olga Yu Fedorenko, Arkadiy V. Semke, Nikolay A. Bokhan, Elena G. Kornetova, Lubov D. Rakhmazova, Bob Wilffert, Anton J.M. Loonen

Research output: Contribution to journalArticle

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Abstract

Background Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin production is regulated by an alternative promoter, which contains the functional single nucleotide polymorphism − 1149 G/T (rs1341239). We examined whether this polymorphism was associated with hyperprolactinemia in patients with schizophrenia. Method We recruited 443 patients with schizophrenia and 126 healthy controls. The functional polymorphism − 1149 G/T (rs1341239) in the prolactin gene was genotyped with multiplexed primer extension, combined with MALDI-TOF mass spectrometry. Genotype and allele frequencies were compared between groups with the χ2 test and logistic regression models adjusting for covariates. Results The frequency of genotypes and alleles in patients with schizophrenia did not differ from those in control subjects. A comparison between patients with schizophrenia with and without hyperprolactinemia revealed significantly higher frequency of the G allele in patients with hyperprolactinemia than in patients without it (χ2 = 7.25; p = 0.007; OR = 1.44 [1.10–1.89]). Accordingly, patients with hyperprolactinemia carried the GG genotype more frequently than patients without hyperprolactinemia (χ2 = 9.49; p = 0.009). This association remained significant after adjusting the estimates for such covariates as sex, age, duration of the diseases and the dose of chlorpromazine equivalents. Conclusion This study revealed a significant association between the polymorphic variant rs1341239 and the development of hyperprolactinemia in patients with schizophrenia. The serum prolactin concentration in patients with schizophrenia treated with antipsychotics may provide an indication of the activity of the gene that regulates extrapituitary prolactin production which is believed to play a role in the immune system.

Original languageEnglish
Pages (from-to)110-114
Number of pages5
JournalSchizophrenia Research
Volume182
DOIs
Publication statusPublished - 1 Apr 2017

Fingerprint

Hyperprolactinemia
Prolactin
Antipsychotic Agents
Schizophrenia
Genes
Gene Frequency
Genotype
Logistic Models
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Chlorpromazine
Autoimmune Diseases
Single Nucleotide Polymorphism
Immune System
Mass Spectrometry
Cytokines

Keywords

  • Cytokines
  • Hyperprolactinemia
  • PRL
  • Prolactin
  • Schizophrenia
  • –1149 G/T polymorphism

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Prolactin gene polymorphism (− 1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics. / Ivanova, Svetlana A.; Osmanova, Diana Z.; Boiko, Anastasia S.; Pozhidaev, Ivan V.; Freidin, Maxim B.; Fedorenko, Olga Yu; Semke, Arkadiy V.; Bokhan, Nikolay A.; Kornetova, Elena G.; Rakhmazova, Lubov D.; Wilffert, Bob; Loonen, Anton J.M.

In: Schizophrenia Research, Vol. 182, 01.04.2017, p. 110-114.

Research output: Contribution to journalArticle

Ivanova, SA, Osmanova, DZ, Boiko, AS, Pozhidaev, IV, Freidin, MB, Fedorenko, OY, Semke, AV, Bokhan, NA, Kornetova, EG, Rakhmazova, LD, Wilffert, B & Loonen, AJM 2017, 'Prolactin gene polymorphism (− 1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics', Schizophrenia Research, vol. 182, pp. 110-114. https://doi.org/10.1016/j.schres.2016.10.029
Ivanova, Svetlana A. ; Osmanova, Diana Z. ; Boiko, Anastasia S. ; Pozhidaev, Ivan V. ; Freidin, Maxim B. ; Fedorenko, Olga Yu ; Semke, Arkadiy V. ; Bokhan, Nikolay A. ; Kornetova, Elena G. ; Rakhmazova, Lubov D. ; Wilffert, Bob ; Loonen, Anton J.M. / Prolactin gene polymorphism (− 1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics. In: Schizophrenia Research. 2017 ; Vol. 182. pp. 110-114.
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abstract = "Background Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin production is regulated by an alternative promoter, which contains the functional single nucleotide polymorphism − 1149 G/T (rs1341239). We examined whether this polymorphism was associated with hyperprolactinemia in patients with schizophrenia. Method We recruited 443 patients with schizophrenia and 126 healthy controls. The functional polymorphism − 1149 G/T (rs1341239) in the prolactin gene was genotyped with multiplexed primer extension, combined with MALDI-TOF mass spectrometry. Genotype and allele frequencies were compared between groups with the χ2 test and logistic regression models adjusting for covariates. Results The frequency of genotypes and alleles in patients with schizophrenia did not differ from those in control subjects. A comparison between patients with schizophrenia with and without hyperprolactinemia revealed significantly higher frequency of the G allele in patients with hyperprolactinemia than in patients without it (χ2 = 7.25; p = 0.007; OR = 1.44 [1.10–1.89]). Accordingly, patients with hyperprolactinemia carried the GG genotype more frequently than patients without hyperprolactinemia (χ2 = 9.49; p = 0.009). This association remained significant after adjusting the estimates for such covariates as sex, age, duration of the diseases and the dose of chlorpromazine equivalents. Conclusion This study revealed a significant association between the polymorphic variant rs1341239 and the development of hyperprolactinemia in patients with schizophrenia. The serum prolactin concentration in patients with schizophrenia treated with antipsychotics may provide an indication of the activity of the gene that regulates extrapituitary prolactin production which is believed to play a role in the immune system.",
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AU - Ivanova, Svetlana A.

AU - Osmanova, Diana Z.

AU - Boiko, Anastasia S.

AU - Pozhidaev, Ivan V.

AU - Freidin, Maxim B.

AU - Fedorenko, Olga Yu

AU - Semke, Arkadiy V.

AU - Bokhan, Nikolay A.

AU - Kornetova, Elena G.

AU - Rakhmazova, Lubov D.

AU - Wilffert, Bob

AU - Loonen, Anton J.M.

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N2 - Background Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin production is regulated by an alternative promoter, which contains the functional single nucleotide polymorphism − 1149 G/T (rs1341239). We examined whether this polymorphism was associated with hyperprolactinemia in patients with schizophrenia. Method We recruited 443 patients with schizophrenia and 126 healthy controls. The functional polymorphism − 1149 G/T (rs1341239) in the prolactin gene was genotyped with multiplexed primer extension, combined with MALDI-TOF mass spectrometry. Genotype and allele frequencies were compared between groups with the χ2 test and logistic regression models adjusting for covariates. Results The frequency of genotypes and alleles in patients with schizophrenia did not differ from those in control subjects. A comparison between patients with schizophrenia with and without hyperprolactinemia revealed significantly higher frequency of the G allele in patients with hyperprolactinemia than in patients without it (χ2 = 7.25; p = 0.007; OR = 1.44 [1.10–1.89]). Accordingly, patients with hyperprolactinemia carried the GG genotype more frequently than patients without hyperprolactinemia (χ2 = 9.49; p = 0.009). This association remained significant after adjusting the estimates for such covariates as sex, age, duration of the diseases and the dose of chlorpromazine equivalents. Conclusion This study revealed a significant association between the polymorphic variant rs1341239 and the development of hyperprolactinemia in patients with schizophrenia. The serum prolactin concentration in patients with schizophrenia treated with antipsychotics may provide an indication of the activity of the gene that regulates extrapituitary prolactin production which is believed to play a role in the immune system.

AB - Background Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin production is regulated by an alternative promoter, which contains the functional single nucleotide polymorphism − 1149 G/T (rs1341239). We examined whether this polymorphism was associated with hyperprolactinemia in patients with schizophrenia. Method We recruited 443 patients with schizophrenia and 126 healthy controls. The functional polymorphism − 1149 G/T (rs1341239) in the prolactin gene was genotyped with multiplexed primer extension, combined with MALDI-TOF mass spectrometry. Genotype and allele frequencies were compared between groups with the χ2 test and logistic regression models adjusting for covariates. Results The frequency of genotypes and alleles in patients with schizophrenia did not differ from those in control subjects. A comparison between patients with schizophrenia with and without hyperprolactinemia revealed significantly higher frequency of the G allele in patients with hyperprolactinemia than in patients without it (χ2 = 7.25; p = 0.007; OR = 1.44 [1.10–1.89]). Accordingly, patients with hyperprolactinemia carried the GG genotype more frequently than patients without hyperprolactinemia (χ2 = 9.49; p = 0.009). This association remained significant after adjusting the estimates for such covariates as sex, age, duration of the diseases and the dose of chlorpromazine equivalents. Conclusion This study revealed a significant association between the polymorphic variant rs1341239 and the development of hyperprolactinemia in patients with schizophrenia. The serum prolactin concentration in patients with schizophrenia treated with antipsychotics may provide an indication of the activity of the gene that regulates extrapituitary prolactin production which is believed to play a role in the immune system.

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KW - Hyperprolactinemia

KW - PRL

KW - Prolactin

KW - Schizophrenia

KW - –1149 G/T polymorphism

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