Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Abstract

BackgroundA number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.MethodsPublished literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.ResultsA total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm2, 95% CI = 0.01-0.03, P < 10-4; at femur neck (FN): WMD = 0.01g/cm2, 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm2, 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm2, 95% CI = 0.02-0.03, P < 10-5; WMD at FN = 0.01g/cm2, 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm2, 95% CI = 0.01-0.05, P = 0.005).ConclusionThis meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.

TCF-1-mediated Wnt signaling regulates Paneth cell innate immune defense effectors HD-5 and -6: implications for Crohn's disease

“…This could be due to the fact the LRP5 gene seems to be very heterogeneous in the studied populations. An at least partial explanation for this observation could also be the essential role that the protein plays in skeletal homeostasis and some of the bone density related variability and diseases within populations seem to be for example linked to SNPs in LRP5 (Yi et al 2013). Furthermore, familial exudative vitreoretinopathy has also been linked to mutations in this gene (Toomes et al 2004).…”

Association of ACTN3 polymorphisms with BMD, and physical fitness of elderly women

“…Additionally, the rs2275913 (−197G>A) polymorphism of the interleukin-17 (IL-17) gene stimulates osteoblasts to synthesize prostaglandin E2 and to express the receptor activator of nuclear factor κ-B ligand (RANKL), there by affecting osteoclastogenesis5 ) . Moreover, the low-density lipoprotein receptor-related protein 5 (LRP5)6 ) gene, Q233R of the leptin receptor gene7 ) , and the Filamin B gene (FLNB)8 ) are also reported to be genetic factors associated with BMD.…”

Arterial calcification, atherosclerosis and osteoporosis: only clinical associations or a genetic platform?

“…В метаанализе Canto-Cetina T, et al (2013), которые изучили влияние ОНП rs3736228 гена LRP5 на показатели МПК различных участков скелета у женщин в постменопаузе, были подтверждены результаты более ранних исследований, свидетельствующих, что лица с генотипом АА полиморфизма A1330V гена LRP5 имеют значительно более высокие показатели МПК ШБ и ПОП, чем обладатели AV и VV аллелей [52]. Метаанализ, объединивший результаты 19 исследований (n=25773), продемонстрировал, что лица с генотипом АА полиморфизма A1330V гена LRP5 по сравнению с остальными имеют более высокие показатели МПК в ПОП (на 200 мг/см 2 ) и ШБ (на 100 мг/см 2 ) [53]. При обследовании 1043 женщин без переломов (возраст 51-90 лет) и 394 женщин с переломами ШБ (возраст 60-90 лет) были обнаружены ассоциации ОНП в генах LRP5 (rs4988321) и LRP6 (rs11054704, rs2302685, rs10845493) с низкими значениями МПК и переломами позвонков [54].…”