title: Relationship between vitamin D receptor (VDR) polymorphisms and the efficacy of recombinant human growth hormone (rhGH) treatment in children with idiopathic short stature.
abstract: Polymorphisms in the vitamin D receptor (VDR) gene are associated with idiopathic short stature (ISS) in several countries. This study aimed to identify a possible correlation between polymorphisms in the VDR promoter in Chinese children with ISS and the efficacy of the recombinant human growth hormone (rhGH) treatment. Pre-pubertal children with ISS and healthy age- and gender-matched children (N = 95 each) were enrolled in this study. Two single nucleotide polymorphisms (SNPs) in the VDR promoter (rs11568820 at the Cdx-2-binding site upstream of exon 1e and rs4516035 at -1012 upstream of exon 1a) were typed. The growth velocity, standard deviation score (SDS) of height for chronological age, height SDS for bone age, predicted adult height, and serum insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) levels of the ISS patients were determined before and 6 months after rhGH treatment. No significant differences were observed in the genotype frequencies between the ISS cases and controls. After rhGH treatment, the growth velocity of the A/G genotype at the Cdx-2-binding site SNP locus was significantly higher than that of the G/G genotype; the IGF-1 and IGFBP-3 levels were also higher in the treated group than the untreated group. However, these changes were independent of the VDR-promoter genotype. Polymorphisms in the VDR promoter may not result in the pathogenesis of ISS in Chinese children. The A/G genotype showed a significantly higher growth velocity than the G/G genotype, and may represent a short-term marker of growth potential.
authors.affiliation: Pediatric Endocrinology Clinic, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 3Zhengzhou Foreign Language School, Zhengzhou, Henan, China.
authors.forename: X P
authors.initials: XP
authors.lastname: Luo
authors.affiliation: Pediatric Endocrinology Clinic, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: L X
authors.initials: LX
authors.lastname: Cai
authors.affiliation: Pediatric Endocrinology Clinic, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Cui
authors.affiliation: Pediatric Endocrinology Clinic, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, UIC College of Medicine, Chicago, IL, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Luo
mesh_terms: D001665:Binding Sites; D001827:Body Height / Q000187:drug effects / Q000235:genetics; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D002648:Child; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018167:Receptors, Calcitriol; D011994:Recombinant Proteins; C579457:VDR protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I