title: Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism.
abstract: We evaluated bone mineralization and metabolism changes related to vitamin D receptor (VDR) polymorphic genotypes in children with juvenile idiopathic arthritis. One hundred and ninety eight children (82 boys and 116 girls) were included in our study. Bone mineral density (BMD) was measured by lumbar spine DXA. Osteocalcin, CTX, parathyroid hormone, total and ionized calcium, inorganic phosphate, total alkaline phosphatase activity was utilized for assessment of bone metabolism. Molecular testing: TaqI (rs731236) and Cdx2 (rs11568820) polymorphisms of VDR were detected by RFLP. No differences in TaqI and Cdx2 haplotypes, genotypes and alleles distribution related with normal and low BMD (Zscore <-2SD) were found. Children with low linear growth (<10th percentile) had more allele T-contained genotypes of TagI VDR (p = 0.037), compare with medium or high linear growth children. Children with high linear growth (>90th percentile) had the highest frequency of allele A-contained genotypes (GA+AA) of Cdx2 VDR (p = 0.009). Girls with TT TaqI VDR, who never been treated by glucocorticoides had lower BMD-Zscore than C allele carriers (TT = -0.94SD [IQR: -2.1;-0.5], TC+CC = -0.62SD [IQR: -1.26;0.39], p = 0.03). Girls with Tanner I with TT had higher total and ionized Ca level than carriers of C allele (Ca: TT = 2.43 ± 0.15 mmol/l, TC+CC = 2.28 ± 0.2 mmol/l, p = 0.024; Ca(2+): TT = 1.15 ± 0.08 mmol/l, TC+CC = 1.06 ± 0.13 mmol/l, p = 0.026). Presence of TT genotype negatively correlated with BMD-Zscore (r = -0.28, p = 0.04), and positively with frequency of LBMD (r = 0.3, p = 0.037). Boy with GG Cdx2 genotype had lower total Ca (GG = 2.3 ± 0.17 mmol/l, GA+AA = 2.43 ± 0.17 mmol/l, p = 0.004) compare with carriers of A allele. Pubertal boys (Tanner IV-V) with GG had higher CTX (GG = 1.75 ± 0.11 ng/ml, GA+AA = 1.06 ± 0.07 ng/ml, p = 0.04. TT genotype of TaqI and GG genotype of Cdx2 VDR is a negative factor impact bone mineralization metabolism and linear growth.
authors.affiliation: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation, kost-mikhail@yandex.ru.
authors.forename: M M
authors.initials: MM
authors.lastname: Kostik
authors.forename: A M
authors.initials: AM
authors.lastname: Smirnov
authors.forename: G S
authors.initials: GS
authors.lastname: Demin
authors.forename: L A
authors.initials: LA
authors.lastname: Scheplyagina
authors.forename: V I
authors.initials: VI
authors.lastname: Larionova
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000378:metabolism*; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D015675:Osteocalcin; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; D015675:Osteocalcin