title: Genetic polymorphisms of collagen type I α1 chain (COL1A1) gene increase the frequency of low bone mineral density in the subgroup of children with juvenile idiopathic arthritis.
abstract: BACKGROUND
  Collagen type I is one of the key proteins involved in the maturation, development and mineralization of bone. Genetic polymorphisms of collagen type I alpha-1 chain (COL1A1) gene are associated with low bone mineral density and higher risk of fractures in adults and children. We hypothesize that the polymorphic alleles and genotypes of COL1A1 gene influence bone mineralization and metabolism in children with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  We recruited 196 children with JIA in our study. Bone mineral density (BMD) was measured by lumbar spine dual-energy X-ray absorptiometry. Osteocalcin, Ca, Ca2+ and inorganic phosphate (Pi) were utilized for the assessment of bone metabolism. Molecular testing: Sp1 (rs1800012) and -1997G/T (rs1107946) polymorphisms of COL1A1 gene were detected RFLP.
  
  
  RESULTS
  No differences in genotype, allele and haplotype distribution of COL1A1 were detected among children with normal and low BMD (LBMD; <-2 standard deviation). The presence of GG genotype of Sp1 increased the incidence of LBMD in Tanner II to III children (odds ratio (OR) = 9.7 [95% confidence interval (CI), 1.2; 81.7], p = 0.02) as well as GG genotype of -1997G/T increased the frequency of LBMD in Tanner IV to V children (OR = 4.5 [95% CI, 0.9; 22.0], p = 0.048). Tanner I children with -1997GG genotype had lower Ca2+ and osteocalcin and higher Pi compared with carriers of -1997Т allele. Tanner IV to V children with -1997GG genotype had lower BMD and BMD-Z score than carriers of -1997Т.
  
  
  CONCLUSIONS
  The evaluation of the biologic effects of the GG Sp1 and GG of -1997G/T polymorphism of COL1A1 has shown negative effect on BMD and mineral turnover related to pubertal stage.
authors.affiliation: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Russia.
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Kostik
authors.affiliation: Gene, Ltd, Saint-Petersburg 194156, Russian Federation.
authors.forename: Arseniy M
authors.initials: AM
authors.lastname: Smirnov
authors.affiliation: Genetic systems, Ltd, Saint-Petersburg 195027, Russian Federation.
authors.forename: Grigory S
authors.initials: GS
authors.lastname: Demin
authors.affiliation: Department of biochemistry, Diagnostic Center#1 for adults, Saint-Petersburg, 194354, Russian Federation.
authors.forename: Marina M
authors.initials: MM
authors.lastname: Mnuskina
authors.affiliation: Moscow scientific and research clinical institute named M.F, Vladimirskiy, Moscow 129110, Russian Federation.
authors.forename: Larisa A
authors.initials: LA
authors.lastname: Scheplyagina
authors.affiliation: Department of molecular diagnostics, Turner's Scientific and Research Institute for Children's Orthopedics, Saint-Petersburg 196603, Russian Federation.
authors.forename: Valentina I
authors.initials: VI
authors.lastname: Larionova