Association of LRP5 haplotypes with osteoporosis in Mexican women

Abstract

Osteoporosis is a common health problem in Mexico, so it is essential to investigate the status of different gene polymorphisms that could serve as genetic susceptibility markers in the Mexican population. Genes with a role in bone metabolism are excellent candidates for association studies. In this study were determined the allelic and genotypic frequencies of four polymorphic markers (C/T rs3736228, G/A rs4988321, T/C rs627174 and T/C rs901824) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) and their association with osteoporosis in 100 pos-menopausal osteoporotic Mexican women and their controls, using real time-PCR and TaqMan probes. Only the G/A polymorphism (rs4988321, Val667Met) showed significant differences (p = 0.039) when genotype frequencies were compared. However, when the haplotypes of these four polymorphisms were analyzed, interesting associations became evident. The CGTT haplotype showed significant association with low risk of osteoporosis (OR 0.629; p = 0.007; [95 % CI, 0.448-0.884]), whereas the TACT haplotype was significantly associated with a higher risk of osteoporosis (OR 7.965; p = 0.006; [95 % CI, 1.557-54.775]). Our results supported the association of LRP5 with osteoporosis and showed the potential value of LRP5 haplotypes to identify risk of osteoporosis in Mexican population.

WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening

“…However, although the nonsynonymous rs3736228 in LRP5 and rs2302685 in LRP6 are the most frequently studied SNPs in candidate gene studies Tran et al 2008;Lee et al 2009), they were not associated with BMD in Mexican women. This lack of association is in accordance with the report of Falcón-Ramírez et al (2013), who analyzed rs3736228, rs4988321, rs627174, and rs901824 in the LRP5 gene in a small case-control study of unrelated Mexican women.…”

“…In the Mexican population, specific genetic factors of BMD variation remain largely unknown as only a few candidate gene studies have been reported in reduced samples and/or analyzing few SNPs (Lisker et al 2003;Gómez et al 2007;Magaña et al 2008;Falcón-Ramírez et al 2011;Rojano-Mejía et al 2013;Falcón-Ramírez et al 2013). The aim of the present study was to seek associations of Wnt pathway gene variants with BMD at various skeletal sites in Mexican mestizo postmenopausal women.…”

LRP receptor family member associated bone disease

“…This led them to conclude that this SNP has a significant association with osteoporosis in this population. An equally interesting finding was that when the authors analyzed the haplotypes of these polymorphisms, there was a clear association between osteoporosis in two haplotypes: the CGTT haplotype was related with lower risk of osteoporosis; and the TACT haplotype was significantly associated with higher risk of osteoporosis [57]. …”

Case Control Association Study of WNT Signaling Pathway-related Genes and Osteoporosis Risk Among Chinese Postmenopausal Women

“…LRP5 encodes a transmembrane protein in the WNT signaling pathway and regulates bone mass in humans and mice [40]. Several studies have shown that LRP5 polymorphisms are a determining factor of bone mass [41]. In this study, we rst found that rs2291467, rs11228240 and rs12272917 of LRP5 were signi cantly associated with a decreased risk of osteoporosis and that the relationships were BMI-dependent.…”