Arseniy M Smirnov1, Grigory S Demin2, Marina M Mnuskina3, Larisa A Scheplyagina4, Mikhail M Kostik5, Valentina I Larionova6. 1. Gene, Ltd, Saint-Petersburg 194156, Russian Federation. 2. Genetic systems, Ltd, Saint-Petersburg 195027, Russian Federation. 3. Department of biochemistry, Diagnostic Center#1 for adults, Saint-Petersburg, 194354, Russian Federation. 4. Moscow scientific and research clinical institute named M.F, Vladimirskiy, Moscow 129110, Russian Federation. 5. Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Russia. 6. Department of molecular diagnostics, Turner's Scientific and Research Institute for Children's Orthopedics, Saint-Petersburg 196603, Russian Federation.
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.
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: T L Stewart; P Roschger; B M Misof; V Mann; P Fratzl; K Klaushofer; R Aspden; S H Ralston Journal: Calcif Tissue Int Date: 2005-05-19 Impact factor: 4.333
Authors: Daniel J Lovell; David Glass; Julie Ranz; Sandy Kramer; Bin Huang; Rosa I Sierra; Carol J Henderson; Murray Passo; Brent Graham; Suzanne Bowyer; Gloria Higgins; Robert Rennebohm; Kenneth N Schikler; Edward Giannini Journal: Arthritis Rheum Date: 2006-07
Authors: Shwan Khoschnau; Håkan Melhus; Annica Jacobson; Hans Rahme; Henrik Bengtsson; Eva Ribom; Elin Grundberg; Hans Mallmin; Karl Michaëlsson Journal: Am J Sports Med Date: 2008-07-31 Impact factor: 6.202
Authors: Praval Khanal; Lingxiao He; Adam J Herbert; Georgina K Stebbings; Gladys L Onambele-Pearson; Hans Degens; Christopher I Morse; Martine Thomis; Alun G Williams Journal: Genes (Basel) Date: 2020-12-05 Impact factor: 4.096
Authors: Mika Saito; Michał Ginszt; Ekaterina A Semenova; Myosotis Massidda; Kinga Huminska-Lisowska; Monika Michałowska-Sawczyn; Hiroki Homma; Paweł Cięszczyk; Takanobu Okamoto; Andrey K Larin; Edward V Generozov; Piotr Majcher; Koichi Nakazato; Ildus I Ahmetov; Naoki Kikuchi Journal: Genes (Basel) Date: 2022-02-23 Impact factor: 4.141