Morteza DEHGHAN, Razieh POURAHMAD-JAKTAJI

Sp1 binding site polymorphism of a collagen gene (rs 1800012) in womenaged 45 and over and its association with bone density

Background/aim: Sp1 polymorphism of type I collagen genes is accompanied with bone c??ollagen disorders and severe clinical phenotypes such as osteogenesis imperfecta. The aim of this study was to study the association between COLIA1 Sp1 polymorphism and bone density rate. Materials and methods: In this descriptive, analytical study conducted in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol-chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. Results: The genotype distribution of Sp1 polymorphism for the SS, Ss, and ss genotypes was 57.1%, 31.4%, and 11.4%, respectively, in the control group and 9.2%, 75.4%, and 15.4%, respectively, in the patients. Statistically, Sp1 polymorphism in patients had a significant deviation (P = 0.001, ?2 = 34.25) and there was no Hardy-Weinberg equilibrium. In the control group, there was no significant deviation for Sp1 polymorphism (P = 0.226, ?2 = 2.97). Sp1 polymorphism was significantly associated with bone density. Women with the SS genotype had the highest bone density. Conclusion: Sp1 gene polymorphism is associated with bone density rate in women aged 45 and over, and is more commonly observed in homozygosity. Determining this genotype's polymorphism is valuable to identify the women at risk of developing osteoporosis.

Anahtar Kelimeler:

Bone mineral density, collagen type 1?1 Sp1 polymorphism, osteoporosis, polymerase chain reaction

Sp1 binding site polymorphism of a collagen gene (rs 1800012) in womenaged 45 and over and its association with bone density

Keywords:

Bone mineral density, collagen type 1?1 Sp1 polymorphism, osteoporosis, polymerase chain reaction,

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Siris ES, Selby PL, Saag KG, Borgström F, Herings RMC, Silverman SL. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 2009; 122: S3–S13.
Gronholz MJ. Prevention, diagnosis, and management of osteoporosis-related fracture: a multifactoral osteopathic approach. J Am Osteopath Assoc 2008; 108: 575–585.
Kung AW, Huang QY. Genetic and environmental determinants of osteoporosis. J Musculoskelet Neuronal Interact 2007; 7: 26– 32.
Duncan EL, Brown MA. Genetic studies in osteoporosis – the end of the beginning. Arthritis Res Ther 2008; 10: 214.
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312: 1254–1259.
Gong G, Haynatzki G, Haynatzka V, Howell R, Kosoko-Lasaki S, Fu YX, Yu F, Gallagher JC, Wilson MR. Bone mineral density-affecting genes in Africans. J Natl Med Assoc 2006; 98: 1102–1108.
Goodman HM. Basic Medical Endocrinology. 4th ed. New York, NY, USA: Academic Press; 2009.
Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol 2007; 13: 3056–3062.
McGuigan FE, Armbrecht G, Smith R, Felsenberg D, Reid DM, Ralston SH. Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: a prospective, population-based study in men and women. Osteoporos Int 2001; 12: 91–96.
Jinnin M. Mechanisms of skin fibrosis in systemic sclerosis. J Dermatol 2010; 37: 11–25.
Xu XH, Dong SS, Guo Y, Yang TL, Lei SF, Papasian CJ, Zhao M, Deng HW. Molecular genetic studies of gene identification for osteoporosis: the 2009 update. Endocr Rev 2010; 31: 447–505.
Marini F, Parri S, Masi L, Ciuffi S, Guazzini A, Fabbri S, Luzi E, Cianferotti L, Brandi ML. COL1A1 Sp1 variation and bone phenotypes in an Italian population. Clin Cases Miner Bone Metab 2013; 10: 133–138.
Liu YZ, Liu YJ, Recker RR, Deng HW. Molecular studies of identification of genes for osteoporosis: the 2002 update. J Endocrinol 2003; 177: 147–196.
Langdahl BL, Uitterlinden AG, Ralston SH, Trikalinos TA, Balcells S, Brandi ML, Scollen S, Lips P, Lorenc R, Obermayer- Pietsch B et al. Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone 2008; 42: 969–981.
Gennari L, Merlotti D, De Paola V, Calabro A, Becherini L, Martini G, Nuti R. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 2005; 161: 307–320.
Jin H, van’t Hof RJ, Albagha OM, Ralston SH. Promoter and intron 1 polymorphisms of COL1A1 interact to regulate transcription and susceptibility to osteoporosis. Hum Mol Genet 2009; 18: 2729–2738.
Marini F, Brandi ML. Genetic determinants of osteoporosis: common bases to cardiovascular diseases? Int J Hypertens 2010; article 394579.
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; 107: 899–907.
Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D. Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 2007; 8: S14.
Braga V, Mottes M, Mirandola S, Lisi V, Malerba G, Sartori L, Bianchi G, Gatti D, Rossini M, Bianchini D et al. Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women. Calcif Tissue Int 2000; 67: 361–366.
Rojerio AL. The primenopause. Clin Obst Gynecol 1998; 41: 895–897.
Dale J, Schantz M. Purification and separation of nucleic acids. In: Dale JW, Schantz MV. From Genes to Genomes. 2nd ed. West Sussex, UK: John Wiley; 2002. pp 31–33.
Rychlik W. New algorithm for determining primer efficiency in PCR and sequencing. J NIH Res 1994; 6: 11.
Walker JM, Rapley R. Molecular Biology and Biotechnology. 4th ed. Cambridge, UK: Royal Society of Chemistry; 2000.
Bundred NJ, Campbell ID, Davidson N, DeBoer RH, Eidtmann H, Monnier A, Neven P, von Minckwitz G, Miller JC, Schenk NL et al. Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST study results. Cancer 2008; 112: 1001–1010.
Abassi M, Hassani S, Sheikholeslami H, Alizadeh S, Rashvand Z, Yazdi Z, Najafipour R. Association between vitamin D receptor Apa1 and Taq1 genes polymorphism and osteoporosis in postmenopausal women. J Qazvin Univ Med Sci 2012; 16: 4–10.
Ji GR, Yao M, Sun CY, Zhang L, Han Z. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta- analysis. J Int Med Res 2009; 37: 1725–1732.
Ralston SH, de Crombrugghe B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 2006; 20: 2492–2506.
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; 14: 203–205.
Marozik P, Mosse I, Ameliyanovich M, Rudenka E, Alekna V, Tamulaitienė M. Molecular and genetic mechanisms of predisposition to osteoporosis. Gerontologija 2011; 12: 250– 258.
Langdahl BL, Ralston SH, Grant SF, Eriksen EF. An Sp1 binding site polymorphism in the COLIA1 gene predicts osteoporotic fractures in both men and women. J Bone Miner Res 1998; 13: 1384–1389.
Weichetova M, Stepan JJ, Haas T, Michalska D. The risk of Colles’ fracture is associated with the collagen I alpha1 Sp1 polymorphism and ultrasound transmission velocity in the calcaneus only in heavier postmenopausal women. Calcif Tissue Int 2005; 76: 98–106.
Nguyen TV, Esteban LM, White CP, Grant SF, Center JR, Gardiner EM, Eisman JA. Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women. J Clin Endocrinol Metab 2005; 90: 6575–6579.
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; 81: 18–25.
Jin H, Stewart TL, Hof RV, Reid DM, Aspden RM, Ralston S. A rare haplotype in the upstream regulatory region of COL1A1 is associated with reduced bone quality and hip fracture. J Bone Miner Res 2009; 24: 448–454.
Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003; 32: 711–717.
Efstathiadou Z, Tsatsoulis A, Ioannidis JP. Association of collagen I alpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 2001; 16: 1586– 1592.
Ashford RU, Luchetti M, McCloskey EV, Gray RL, Pande KC, Dey A, Kayan K, Ralston SH, Kanis JA. Studies of bone density, quantitative ultrasound, and vertebral fractures in relation to collagen type I alpha 1 alleles in elderly women. Calcif Tissue Int 2001; 68: 348–351.
Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Scollen S, Bustamante M et al. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 2006; 3: e90.
Ji GR, Yao M, Sun CY, Zhang L, Han Z. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta- analysis. J Int Med Res 2009; 37: 1725–1732.
Özbaş H, Onrat ST, Özdamar K. Genetic and environmental factors in human osteoporosis. Mol Biol Rep 2012; 39: 11289– 11296.
Liden M, Wilen B, Ljunghall S, Melhus H. Polymorphism at the Sp 1 binding site in the collagen type I alpha 1 gene does not predict bone mineral density in postmenopausal women in Sweden. Calcif Tissue Int 1998; 63: 293–295.
McClean E, Archbold GP, Taggart HM. Do the COL1A1 and Taq 1 vitamin D receptor polymorphisms have a role in identifying individuals at risk of developing osteoporosis? Ulster Med J 2003; 72: 26–33.
Bandres E, Pombo I, Gonzalez-Huarriz M, Rebollo A, Lopez G, Garcia-Foncillas J. Association between bone mineral density and polymorphisms of the VDR, ERalpha, COL1A1 and CTR genes in Spanish postmenopausal women. J Endocrinol Invest 2005; 28: 312–321.
Tural S, Kara N, Alayli G, Tomak L. Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women. Gene 2013; 515: 167–172.