Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies

Li Bao, Mingzhi Chen, Yong Lei, Zemin Zhou, Huiping Shen, Feng Le, Li Bao, Mingzhi Chen, Yong Lei, Zemin Zhou, Huiping Shen, Feng Le

Abstract

Background: Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear.

Methods: Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016. Data were extracted from the eligible studies, and associations between VDR BsmI polymorphism and BMD in pediatric patients were estimated with weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analysis of ethnicity and sensitivity analyses were used to identify sources of heterogeneity.

Results: A significant difference was observed between VDR BsmI polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No significant relationship was found in the dominant, recessive, or codominant models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45, 95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95% CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25).

Conclusion: Our meta-analysis found that the VDR BsmI genetic polymorphism was correlated with LS BMD level in pediatric patients: compared with those with the B allele, children with the bb genotype were less likely to have lower BMD levels. No significant difference was identified in the pediatric FN BMD levels.

Conflict of interest statement

The authors have no funding and conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flow diagram of eligible studies.
Figure 2
Figure 2
Pooled results of vitamin D receptor BsmI genetic polymorphism on pediatric bone mineral density levels in lumbar spine in the corecessive model.

References

    1. Fukazawa T, Yabe I, Kikuchi S, et al. Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. J Neurol Sci 1999;166:47–52.
    1. Smolders J, Damoiseaux J, Menheere P, et al. Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol 2009;207:117–21.
    1. Paine KM, Paliga JT, Tahiri Y, et al. An assessment of 30-day complications in primary cleft palate repair: a review of the 2012 ACS NSQIP pediatric. Cleft Palate Craniofac J 2016;53:357–62.
    1. Zhao DD, Yu DD, Ren QQ, et al. Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: a meta-analysis. Pediatr Pulmonol 2017;52:423–9.
    1. Ferrari S, Rizzoli R, Slosman D, et al. Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab 1998;83:358–61.
    1. Jones G, Nguyen TV. Associations between maternal peak bone mass and bone mass in prepubertal male and female children. J Bone Miner Res 2000;15:1998–2004.
    1. Slemenda CW, Christian JC, Williams CJ, et al. Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 1991;6:561–7.
    1. Morrison NA, Qi JC, Tokita A, et al. Prediction of BMD from vitamin D receptor alleles. Nature 1994;367:284–7.
    1. Biondi-Zoccai G, Lotrionte M, Landoni G, et al. The rough guide to systematic reviews and meta-analyses. HSR Proc Intensive Care Cardiovasc Anesth 2011;3:161–73.
    1. Ferrari SL, Rizzoli R, Slosman DO, et al. Do dietary calcium and age explain the controversy surrounding the relationship between bone mineral density and vitamin D receptor gene polymorphisms? J Bone Miner Res 1998;13:363–70.
    1. Baroncelli GI, Federico G, Bertelloni S, et al. Vitamin-D receptor genotype does not predict bone mineral density, bone turnover, and growth in prepubertal children. Horm Res 1999;51:150–6.
    1. Nelson DA, Vande Vord PJ, Wooley PH. Polymorphism in the vitamin D receptor gene and bone mass in African-American and white mothers and children: a preliminary report. Ann Rheum Dis 2000;59:626–30.
    1. Arabi A, Mahfoud Z, Zahed L, et al. Effect of age, gender and calciotropic hormones on the relationship between vitamin D receptor gene polymorphisms and bone mineral density. Eur J Clin Nutr 2010;64:383–91.
    1. Jakubowska-Pietkiewicz E, Mlynarski W, Klich I, et al. Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients. Mol Biol Rep 2012;39:6243–50.
    1. Yu Weili WS, Guo J, Zeng Y, et al. Bone mineral density among 9–12 years old Han children and the relation between vitamin D receptor gene polymorphism and bone mineral density. J Xi’an Jiaotong Univ 2008;29:115–7.
    1. Ivanova S, Vasileva L, Ivanova S, et al. Osteoporosis: therapeutic options. Folia Med 2015;57:181–90.
    1. Man PW, van der Meer IM, Lips P, et al. Vitamin D status and bone mineral density in the Chinese population: a review. Arch Osteoporos 2016;11:14.
    1. Palomba S, Orio F, Jr, Russo T, et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporosis Int 2005;16:943–52.
    1. Rass P, Pakozdi A, Lakatos P, et al. Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. Rheumatol Int 2006;26:964–71.
    1. Phabphal K, Geater A, Limapichart K, et al. The association between BsmI polymorphism and bone mineral density in young patients with epilepsy who are taking phenytoin. Epilepsia 2013;54:249–55.
    1. Pouresmaeili F, Jamshidi J, Azargashb E, et al. Association between vitamin D receptor gene BsmI polymorphism and bone mineral density in a population of 146 Iranian women. Cell J 2013;15:75–82.
    1. Uitterlinden AG, Pols HA, Burger H, et al. A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density. J Bone Miner Res 1996;11:1241–8.
    1. Fang Y, Rivadeneira F, van Meurs JB, et al. Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: a meta-analysis. Bone 2006;39:938–45.
    1. Moran JM, Pedrera-Canal M, Rodriguez-Velasco FJ, et al. Lack of association of vitamin D receptor BsmI gene polymorphism with bone mineral density in Spanish postmenopausal women. PeerJ 2015;3:e953.

Source: PubMed

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