Indices of growth and vitamin D metabolism in relation to the +1245G>T polymorphism of the COL1A1 GENE in children with idiopathic short stature
DOI:
https://doi.org/10.32782/2077-6594/2024.3/20Keywords:
Idiopathic short stature, children, 1245 G/T (rs1800012) polymorphism of the COL1A1 gene, genotype distributionAbstract
Purpose: the aim of our study was to investigate vitamin D status and auxological parameters in children with idiopathic short stature in relation to the +1245G>T polymorphism of the COL1A1 gene. Materials and methods. A clinical and genetic study of 35 children with idiopathic short stature treated at the V.P. Komisarenko State Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine was performed. Determination of the +1245 G > T (rs1800012) polymorphism of the COL1A1 gene was performed using the polymerase chain reaction method, followed by analysis of the length of restriction fragments detected by agarose gel electrophoresis. The results of the study were statistically analyzed in Excel. Results. The greatest growth retardation was observed in the homozygous G/G genotype, followed by the T/T homozygote, and children heterozygous for the T/G alleles had the least growth retardation among all patients with ISS. Basal GH levels were low in all study groups regardless of genotype, but were lowest in carriers of the T/T homozygous genotype. Growth hormone (GH) levels after stimulation with clonidine were above 10 ng/ml in all subjects, i.e. in line with the norm. The level of HDI-1 in the study subjects was normal, but its lowest level was found in patients with the presence of the heterozygous T/G polymorphism. Conclusions. A significant number of children with idiopathic short stature (65,71%) have a homozygous G/G genotype of the +1245 G/T polymorphism (rs1800012) of the COL1A1 gene, homozygotes for T/T alleles were 2,86% and heterozygotes for T/G alleles were 31,43%. Hypovitaminosis D occurred in all children with idiopathic short stature: deficiency – in children with heterozygous T/G genotype (46,38 ± 3,43 nmol/L), and vitamin D insufficiency – in carriers of homozygous genotypes, namely T/T genotype (70,30 ± 0,00 nmol/L) and homozygous G/G genotype (55,20 ± 4,72 nmol/L).
References
Harrison SR, Li D, Jeffery LE, Raza K, Hewison M. Vitamin D, Autoimmune Disease and Rheumatoid Arthritis. Calcif Tissue Int. 2020 Jan; 106 (1): 58–75. DOI: 10.1007/s00223-019-00577-2.
Grant WB. Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer. Anticancer Res. 2020 Jan; 40 (1): 491–499. DOI: 10.21873/anticanres.13977.
Garfinkel RJ, Dilisio MF, Agrawal DK. Vitamin D and Its Effects on Articular Cartilage and Osteoarthritis. Orthop J Sports Med. 2017 Jun 20; 5 (6): 2325967117711376. DOI: 10.1177/2325967117711376.
Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014 May; 14 (5): 342–57. DOI: 10.1038/nrc3691.
Wacker M, Holick MF. Vitamin D – effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013 Jan 10; 5 (1): 111–48. DOI: 10.3390/nu5010111.
Wang TJ. Vitamin D and Cardiovascular Disease. Annu Rev Med. 2016; 67: 261–72. DOI: 10.1146/annurevmed-051214-025146.
Maier GS, Weissenberger M, Rudert M, Roth KE, Horas K. The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology-a narrative overview of the literature. Ann Transl Med. 2021 Jun; 9 (11): 942. DOI: 10.21037/atm-21-779.
Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev EndocrMetabDisord. 2017 Jun; 18 (2): 153–165. DOI: 10.1007/s11154-017-9424-1.
Michelson JD, Charlson MD. Vitamin D Status in an Elective Orthopedic Surgical Population. Foot Ankle Int. 2016 Feb; 37 (2): 186–91. DOI: 10.1177/1071100715609054.
Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, El-Hajj Fuleihan G, Josse RG, Lips P, Morales-Torres J. IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009 Nov; 20 (11): 1807–20. DOI: 10.1007/s00198-009-0954-6.
Maier GS, Jakobs P, Roth KE, Kurth AA, Maus U. Is there an epidemic vitamin D deficiency in German orthopaedic patients? ClinOrthopRelat Res. 2013 Sep; 471 (9): 3029–35. DOI: 10.1007/s11999-013-2996-5.
Maier GS, Horas K, Seeger JB, Roth KE, Kurth AA, Maus U. Vitamin D insufficiency in the elderly orthopaedic patient: an epidemic phenomenon. IntOrthop. 2015 Apr; 39 (4): 787–92. DOI: 10.1007/s00264-014-2519-3.
Peng X, Hawthorne M, Vaishnav A, St-Arnaud R, Mehta RG. 25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture. Breast Cancer Res Treat. 2009 Jan; 113 (1): 31–41. DOI: 10.1007/s10549-008-9900-0.
Cross HS, Lipkin M, Kállay E. Nutrients regulate the colonic vitamin D system in mice: relevance for human colon malignancy. J Nutr. 2006 Mar; 136 (3): 561–4. DOI: 10.1093/jn/136.3.561.
Rohan JN, Weigel NL. 1Alpha, 25-dihydroxyvitamin D3 reduces c-Myc expression, inhibiting proliferation and causing G1 accumulation in C4-2 prostate cancer cells. Endocrinology. 2009 May; 150 (5): 2046–54. DOI: 10.1210/en.2008-139.5
Ebert R, Schütze N, Adamski J, Jakob F. Vitamin D signaling is modulated on multiple levels in health and disease. Mol Cell Endocrinol. 2006 Mar 27; 248 (1–2): 149–59. DOI: 10.1016/j.mce.2005.11.039.
Klotz B, Mentrup B, Regensburger M, Zeck S, Schneidereit J, Schupp N, Linden C, Merz C, Ebert R, Jakob F. 1,25-dihydroxyvitamin D3 treatment delays cellular aging in human mesenchymal stem cells while maintaining their multipotent capacity. PLoS One. 2012; 7 (1): e29959. DOI: 10.1371/journal.pone.0029959.
Horas K, Maier G, Jakob F, Maus U, Kurth A, Jakuscheit A, Rudert M, Holzapfel BM. High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors. Cancer Invest. 2017 Sep 14; 35 (8): 562–568. DOI: 10.1080/07357907.2017.1351985.
Rapaport R, Wit JM, Savage MO. Growth failure: “idiopathic” only after a detailed diagnostic evaluation. Endocr Connect. 2021 Mar; 10 (3): R125 – R138. DOI: 10.1530/EC-20-0585.
Ungureanu MC, Hrisca A, Caba L, Teodoriu L, Bilha S, Preda C, Leustean L. SHOX Deletion and Idiopathic Short Stature: What Does the Clinician Need to Know? Case Series Report. Diagnostics (Basel). 2022 Dec 29; 13 (1): 105. DOI: 10.3390/diagnostics13010105.
Erdogan MO, Yıldız H, Artan S, Solak M, Taşcıoğlu F, Dündar U, Eser B, Colak E. Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporos Int. 2011 Apr; 22 (4): 1219–25. DOI: 10.1007/s00198-010-1312-4.
Hubacek JA, Weichetova M, Bohuslavova R, Skodova Z, Adámkova V, Stepan JJ. Genetic polymorphisms of TGF-beta, PAI-1, and COL1A-1, and determination of bone mineral density in Caucasian females. EndocrRegul. 2006 Sep; 40 (3): 77–81.
Ralston SH, de Crombrugghe B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev. 2006 Sep 15; 20 (18): 2492–506. DOI: 10.1101/gad.1449506.
Soibam D, Singh TA, Nandy P, Dewan SK, Baruah A. Sp1 Binding Site Polymorphism at COL1A1 Gene and Its Relation to Bone Mineral Density for Osteoporosis Risk Factor Among the Sikkimese Men and Women of Northeast India. Indian J ClinBiochem. 2019 Apr; 34 (2): 230–233. DOI: 10.1007/s12291-017-0728-4.
Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest. 2001 Apr; 107 (7): 899–907. DOI: 10.1172/JCI10347.
Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone. 2003 Jun; 32 (6): 711–7. DOI: 10.1016/s8756-3282(03)00087-5.
Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet. 1996 Oct; 14 (2): 203–5. DOI: 10.1038/ng1096-203.
Yazdanpanah N, Rivadeneira F, van Meurs JB, Zillikens MC, Arp P, Hofman A, van Duijn CM, Pols HA, Uitterlinden AG. The 1997 G/T and Sp1 polymorphisms in the collagen type I alpha1 (COLIA1) gene in relation to changes in femoral neck bone mineral density and the risk of fracture in the elderly: the Rotterdam study. Calcif Tissue Int. 2007 Jul; 81 (1): 18–25. DOI: 10.1007/s00223-007-9033-1.
Zhang LQ, Liu H, Huang XF. Relation of JAGGED 1 and collagen type 1 alpha 1 polymorphisms with bone mineral density in Chinese postmenopausal women. Int J ClinExpPathol. 2014 Sep 15; 7 (10): 7142–7.
Bustamante M, Nogués X, Enjuanes A, Elosua R, García-Giralt N, Pérez-Edo L, Cáceres E, Carreras R, Mellibovsky L, Balcells S, Díez-Pérez A, Grinberg D. COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporos Int. 2007 Feb; 18 (2): 235–43. DOI: 10.1007/s00198-006-0225-8.
