Carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene increases the risk of obesity in infants with phenylketonuria

Miroslaw Bik-Multanowski; Anna Madetko-Talowska; Iwona Betka; Elzbieta Swieczka; Bozena Didycz; Karolina Orchel-Szastak; Kinga Bik-Multanowska; Ewa Starostecka; Joanna Jaglowska; Renata Mozrzymas; Joanna Zolkowska; Katarzyna Chyz; Dorota Korycinska-Chaaban

doi:10.1016/j.ymgmr.2020.100640

Carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene increases the risk of obesity in infants with phenylketonuria

Mol Genet Metab Rep. 2020 Aug 21:25:100640. doi: 10.1016/j.ymgmr.2020.100640. eCollection 2020 Dec.

Affiliations

¹ Department of Medical Genetics, Jagiellonian University Medical College, Krakow, Poland.
² Department of Endocrinology and Metabolic Diseases, Polish Mother's Health Memorial Institute, Lodz, Poland.
³ Department Pediatrics, Hematology and Oncology, Medical University, Gdansk, Poland.
⁴ Voivodeship Hospital, Wroclaw, Poland.
⁵ Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.

Abstract

Purpose: Phenylketonuria (PKU) can be effectively treated with the use of a low-phenylalanine diet. However, some patients become overweight despite proper dietary treatment. We hypothesized that this phenomenon could be explained by the presence of specific variants within the genes involved in phenylalanine transport or in the phenylalanine transamination/oxygenation pathway.

Methods: We selected a clinically homogenous group of 100 infants with PKU and assessed their growth patterns in the context of dietary phenylalanine tolerance. Next, within the sample, we performed exome sequencing and assessed a potential relationship between the observed phenotypical variability and the presence of structural variants in a priori selected genes of interest.

Results: We detected a highly significant association between overweight and carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene, which encodes the main transmembrane transporter of large neutral amino acids and of thyroid hormones.

Conclusions: Our findings suggest a pharmacogenetic effect of the relatively common rs113883650/rs2287120 haplotype of the SLC7A5 gene. This can have practical implications for patients with PKU, since treatment protocols need to be reassessed to better prevent overweight in the carriers of the above variant.

Keywords: Metabolism; Obesity; Personalized medicine; Pharmacogenomics; WES.