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UGT1A1 polymorphisms associated with prolactin response in risperidone-treated children and adolescents with autism spectrum disorder

The Pharmacogenomics Journal volume 18, pages 740–748 (2018)Cite this article

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Abstract

The aim of this study was to investigate the association of drug-metabolizing enzyme and transporter (DMET) polymorphisms with the risperidone-induced prolactin response using an overlapping gene model between serum prolactin level and hyperprolactinemia in autism spectrum disorder (ASD) patients. Eighty-four ASD patients who were receiving risperidone for at least 1 month were recruited and then assigned to either the normal prolactin group or the hyperprolactinemia group based on their serum prolactin level. The genotype profile of 1936 (1931 single nucleotide polymorphisms (SNPs) and 5 copy number variation (CNVs) drug metabolism markers was obtained using the Affymetrix DMET Plus GeneChip microarray platform. Genotypes of SNPs used to test the accuracy of DMET genotype profiling were determined using TaqMan SNP Genotyping Assay kits. Eighty-four patients were selected for the allelic association study after microarray analyses (51 in the normal prolactin group, and 33 in the hyperprolactinemia group). An overlapping allelic association analysis of both analyses discovered five DMET SNPs with a suggestive association (P < 0.05) with risperidone-induced prolactin response. Three UGT1A1 SNPs (UGT1A1*80c.-364C > T, UGT1A1*93 c.-3156G > A, and UGT1A1 c.-2950A > G, showed a suggestive association with the risperidone-induced prolactin response and found to be in complete linkage disequilibrium (D′ value of 1). In this DMET microarray platform, we found three UGT1A1 variants with suggestive evidences of association with the risperidone-induced prolactin response both measured by hyperprolactinemia and by prolactin level. However, due to the lack of validation studies confirmation and further exploration are needed in future pharmacogenomic studies.

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Acknowledgements

Financial support from the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0107/2557) to Yaowaluck Hongkaew and Chonlaphat Sukasem is acknowledged. We thank all the staff in Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital and all the children and adolescents with ASD who participated in the study.

Funding

This study was supported by grants of the (1) the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0107/2557), (2) Pharmacogenomics for Autistic Child Project, Khoon Poom Foundation, The Project of Her Royal Highness Princess Ubonratana Rajakanya Siriwatana Bhanawadee, (3) Office of National Research Council of Thailand, (4) Faculty of Medicine Ramathibodi Hospital, and (5) Mahidol University.

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Authors and Affiliations

  1. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Yaowaluck Hongkaew, Sadeep Medhasi, Apichaya Puangpetch, Natchaya Vanwong, Monpat Chamnanphon & Chonlaphat Sukasem

  2. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand

    Yaowaluck Hongkaew, Sadeep Medhasi, Apichaya Puangpetch, Natchaya Vanwong, Monpat Chamnanphon & Chonlaphat Sukasem

  3. School of Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand

    Sadeep Medhasi

  4. Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Ekawat Pasomsub

  5. Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, Samut Prakan, Thailand

    Nattawat Ngamsamut & Penkhae Limsila

  6. Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

    Chuthamanee Suthisisang

  7. University of Groningen, Department of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, Groningen, The Netherlands

    Bob Wilffert

  8. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Bob Wilffert

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  1. Yaowaluck Hongkaew
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Correspondence to Chonlaphat Sukasem.

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Hongkaew, Y., Medhasi, S., Pasomsub, E. et al. UGT1A1 polymorphisms associated with prolactin response in risperidone-treated children and adolescents with autism spectrum disorder. Pharmacogenomics J 18, 740–748 (2018). https://doi.org/10.1038/s41397-018-0031-7

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