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

Abstract

Background: The WNT signaling pathway is involved in the regulation of bone homeostasis, and the effects of WNT signaling pathway related genes (WLS, WNT16 and LRP5) on osteoporosis risk among Chinese postmenopausal women is still unknown. Hence, we performed a case-control study to assess the association of WNT signaling pathway related genes and osteoporosis risk.Methods: This study involved 1026 women (515 osteoporosis patients and 511 controls) of postmenopausal age who were randomly sampled from Xi'an 630 Hospital, Shaanxi Province, China. Eleven genetic polymorphisms in WLS (rs2566755, rs12407028, rs2566752 and rs7554551), WNT16 (rs3779381, rs3801387, rs917727 and rs7776725) and LRP5 (rs2291467, rs11228240 and rs12272917) were selected and genotyped using the Agena MassARRAY iPLEX system. The association of the genetic polymorphisms and osteoporosis risk was assessed by odds ratios and 95% confidence intervals. The Multifactor Dimensionality Reduction (MDR) method was conducted to analyze SNP-SNP interaction.Results: We found that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) were significantly associated with a decreased risk of osteoporosis in homozygotes, both in recessive and additive models (P < 0.05). Stratification analysis showed that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) significantly decreased the osteoporosis risk in the subgroup of BMI ≤ 24 (P < 0.05) and that individuals carrying a heterozygote genotype of WNT16 polymorphisms (rs3779381, rs3801387, rs917727 and rs7776725) had a higher osteoporosis risk in the subgroup of BMI > 24 (P < 0.05). We observed that three blocks (block 1: rs2566755 and rs12407028, block 2: rs3779381, rs3801387, rs917727 and rs7776725, block 3: rs2291467 and rs11228240), Trs2291467Trs11228240 and Crs2291467Crs11228240 had a strong association with a lower risk of osteoporosis. Additionally, MDR analysis revealed that a four-locus model (rs2566752 and rs2566755 in WLS, rs7776725 in WNT16, rs12272917 in LRP5) was significantly associated with osteoporosis risk. Conclusions: Our findings suggested that WLS, WNT16 and LRP5 genetic polymorphisms were associated with osteoporosis risk among Chinese postmenopausal women.