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

Autor: Paul Tadeo Ríos-Gallardo, Nelly Altamirano-Bustamante, Sara Frías, Benilde García-de-Teresa, Raúl Calzada-León, Silvia Sánchez, Alessandra Carnevale, Edmundo Bonilla, José A. Velázquez-Aragón, Alejandro Valderrama-Hernández, Christian David Alvarado-Araiza, Angélica Martínez, Bertha Molina, Leda Torres, Rehotbevely Barrientos-Rios, Camilo E Villaroel
Rok vydání: 2019
Předmět:
musculoskeletal diseases
Adult
medicine.medical_specialty
Adolescent
Heart malformation
Endocrinology
Diabetes and Metabolism
Gonadal dysgenesis
Turner Syndrome
030209 endocrinology & metabolism
Biology
Kidney
Short stature
Calcitriol receptor
Polymorphism
Single Nucleotide
Thyroiditis
PTPN22
03 medical and health sciences
Young Adult
0302 clinical medicine
Endocrinology
Gene Frequency
Bone Density
Internal medicine
Turner syndrome
medicine
Humans
Vitamin D
Child
Klotho Proteins
Mexico
Genetic Association Studies
Glucuronidase
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
030219 obstetrics & reproductive medicine
Genetic disorder
Obstetrics and Gynecology
Infant
Epistasis
Genetic
Protein Tyrosine Phosphatase
Non-Receptor Type 22
medicine.disease
Bone Diseases
Metabolic
Case-Control Studies
Child
Preschool
Urogenital Abnormalities
Receptors
Calcitriol
Female
medicine.symptom
Metabolic Networks and Pathways
Zdroj: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 35(9)
ISSN: 1473-0766
Popis: 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 PTPN22, VDR, KL, and CYP27B1 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 (VDR), rs9536282 (KL), rs4646536 (CYP27B1), and rs1599971 (PTPN22) 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 (KL) variant and between rs4646536 (CYP27B1) 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 KL, CYP27B1 and VDR 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje