Low bone mineral density and renal malformation in Mexican patients with Turner syndrome are associated with single nucleotide variants in vitamin D-metabolism genes.

Rehotbevely Barrientos-Rios, Sara Frias, José A Velázquez-Aragón, Camilo E Villaroel, Silvia Sánchez, Bertha Molina, Angélica Martínez, Alessandra Carnevale, Benilde García-de-Teresa, Edmundo Bonilla, Christian David Alvarado-Araiza, Alejandro Valderrama-Hernández, Paul Tadeo Ríos-Gallardo, Raúl Calzada-León, Nelly Altamirano-Bustamante, Leda Torres

Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2020;35(9):772-776

PMID: 30887870

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Abstract

Turner syndrome (TS) is a common genetic disorder. TS-phenotype includes short stature, gonadal dysgenesis, cardiac and kidney malformations, low bone mineral density (low-BMD) and thyroiditis. TS-phenotype varies from patient to patient and the cause is not clear, the genomic background may be an important contributor for this variability. Our aim was to identify the association of specific single nucleotide variants in the , , and genes and vitamin D-metabolism, heart malformation, renal malformation, thyroiditis, and low-BMD in 61 Mexican TS-patients. DNA samples were genotyped for SNVs: rs7975232 (), rs9536282 (), rs4646536 (), and rs1599971 () using the KASP assay. Chi-square test under a recessive model and multifactorial dimensionality reduction method were used for analysis. We found a significant association between renal malformation and the rs9536282 () variant and between rs4646536 () and low-BMD, these variants may have modest effects on these characteristics but contribute to the variability of the TS phenotype. In addition, we identified gene-gene interactions between variants in genes , and related to vitamin D-metabolism and low-BMD in TS-patients. Our results support the idea that the genetic background of TS-patients contributes to the clinical variability seen in them.

Address: a Laboratorio de Citogenética, Departamento de Genética Humana, Instituto Nacional de Pediatría , Ciudad de México , Mexico.; b Posgrado en Biología Experimental, Universidad Autónoma Metropolitana , Ciudad de México , Mexico.; c Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Ciudad de México , Mexico.; d Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría , Ciudad de México , Mexico.; e Departamento de Genética Humana, Instituto Nacional de Pediatría , Ciudad de México , Mexico.; f Departamento de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica , Ciudad de México , Mexico.; g Laboratorio de Enfermedades Mendelianas, Instituto Nacional de Medicina Genómica , Ciudad de México , Mexico.; h Servicio de Endocrinología, Instituto Nacional de Pediatría , Ciudad de México , Mexico.

DOI: 10.1080/09513590.2019.1582626

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https://www.tandfonline.com/doi/10.1080/09513590.2...

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https://medlineplus.gov/turnersyndrome.html

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https://figshare.com/articles/by-resource-doi/10.1...

MeSH Terms: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Adolescent, Adult, Bone Density, Bone Diseases, Metabolic, Case-Control Studies, Child, Child, Preschool, Epistasis, Genetic, Female, Gene Frequency, Genetic Association Studies, Glucuronidase, Humans, Infant, Kidney, Klotho Proteins, Metabolic Networks and Pathways, Mexico, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Receptors, Calcitriol, Turner Syndrome, Urogenital Abnormalities, Vitamin D, Young Adult