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Abstract：
OBJECTIVE: To assess LRP5-/6 gene polymorphisms and its association with risk of abnormal bone mass (ABM) in postmenopausal women.
METHODS: The study recruited 166 patients with ABM (case group) and 106 patients with normal bone mass (control group) based on bone mineral density (BMD) results. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the Low-density lipoprotein receptor-related protein 5 (LRP5) gene (rs41494349, rs2306862) and the Low-density lipoprotein receptor-related protein 6 (LRP6) gene (rs10743980, rs2302685) and the subjects\' clinical characteristics of age and menopausal years.
RESULTS: (1) Logistic regression analysis showed that the subjects with the CT or TT genotype at rs2306862 had a higher risk of ABM than those with the CC genotype (OR = 2.353, 95%CI = 1.039-6.186; OR = 2.434, 95%CI = 1.071, 5.531; P < 0.05). The subjects with the TC genotype at rs2302685 had a higher risk of ABM than those with the TT genotype (OR = 2.951, 95%CI = 1.030-8.457, P < 0.05). (2) When taking the three Single-nucleotide polymorphisms (SNPs) together, the accuracy was the highest with the cross-validation consistency of 10/10 (OR = 1.504, 95%CI:1.092-2.073, P < 0.05), indicating that the LRP5 rs41494349 and LRP6 rs10743980, rs2302685 were interactively associated with the risk of ABM. (3) Linkage disequilibrium (LD) results revealed that the LRP5 (rs41494349,rs2306862) were in strong LD (D\' > 0.9, r2 > 0.3). AC and AT haplotypes were significantly more frequently distributed in the ABM group than in the control group, indicating that subjects carrying the AC and AT haplotypes were associated with an increased risk of ABM (P < 0.01). (4) MDR showed that rs41494349 & rs2302685 & rs10743980 & age were the best model for ABM prediction. The risk of ABM in \"high-risk combination\" was 1.00 times that of \"low-risk combination\"(OR = 1.005, 95%CI: 1.002-1.008, P < 0.05). (5) MDR showed that there was no significant association between any of the SNPs and menopausal years and ABM susceptibility.
CONCLUSIONS: These findings indicate that LRP5-rs2306862 and LRP6-rs2302685 polymorphisms and gene-gene and gene-age interactions may increase the risk of ABM in postmenopausal women. There was no significant association between any of the SNPs and menopausal years and ABM susceptibility.
METHODS: The study recruited 166 patients with ABM (case group) and 106 patients with normal bone mass (control group) based on bone mineral density (BMD) results. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the Low-density lipoprotein receptor-related protein 5 (LRP5) gene (rs41494349, rs2306862) and the Low-density lipoprotein receptor-related protein 6 (LRP6) gene (rs10743980, rs2302685) and the subjects\' clinical characteristics of age and menopausal years.
RESULTS: (1) Logistic regression analysis showed that the subjects with the CT or TT genotype at rs2306862 had a higher risk of ABM than those with the CC genotype (OR = 2.353, 95%CI = 1.039-6.186; OR = 2.434, 95%CI = 1.071, 5.531; P < 0.05). The subjects with the TC genotype at rs2302685 had a higher risk of ABM than those with the TT genotype (OR = 2.951, 95%CI = 1.030-8.457, P < 0.05). (2) When taking the three Single-nucleotide polymorphisms (SNPs) together, the accuracy was the highest with the cross-validation consistency of 10/10 (OR = 1.504, 95%CI:1.092-2.073, P < 0.05), indicating that the LRP5 rs41494349 and LRP6 rs10743980, rs2302685 were interactively associated with the risk of ABM. (3) Linkage disequilibrium (LD) results revealed that the LRP5 (rs41494349,rs2306862) were in strong LD (D\' > 0.9, r2 > 0.3). AC and AT haplotypes were significantly more frequently distributed in the ABM group than in the control group, indicating that subjects carrying the AC and AT haplotypes were associated with an increased risk of ABM (P < 0.01). (4) MDR showed that rs41494349 & rs2302685 & rs10743980 & age were the best model for ABM prediction. The risk of ABM in \"high-risk combination\" was 1.00 times that of \"low-risk combination\"(OR = 1.005, 95%CI: 1.002-1.008, P < 0.05). (5) MDR showed that there was no significant association between any of the SNPs and menopausal years and ABM susceptibility.
CONCLUSIONS: These findings indicate that LRP5-rs2306862 and LRP6-rs2302685 polymorphisms and gene-gene and gene-age interactions may increase the risk of ABM in postmenopausal women. There was no significant association between any of the SNPs and menopausal years and ABM susceptibility.
摘要：
目的：评估LRP5-/6基因多态性及其与绝经后妇女骨量异常（ABM）风险的关系。
方法：本研究根据骨密度（BMD）结果招募了166例ABM患者（病例组）和106例骨量正常的患者（对照组）。多因素降维（MDR）用于分析低密度脂蛋白受体相关蛋白5（LRP5）基因（rs41494349，rs2306862）和低密度脂蛋白受体相关蛋白6（LRP6）基因（rs10743980，rs2302685）与受试者年龄和绝经年龄的临床特征之间的相互作用。
结果：（1）Logistic回归分析显示，rs2306862为CT或TT基因型的受试者患ABM的风险高于CC基因型的受试者（OR=2.353，95CI=1.039-6.186；OR=2.434，95CI=1.071，5.531；P<0.05）。TC基因型rs2302685的受试者发生ABM的风险高于TT基因型（OR=2.951，95CI=1.030-8.457，P<0.05）。（2）当三个单核苷酸多态性（SNP）一起服用时，交叉验证一致性为10/10(OR=1.504,95CI:1.092-2.073,P<0.05),表明LRP5rs41494349和LRP6rs10743980，rs2302685与ABM风险相互作用相关。（3）连锁不平衡（LD）结果表明，LRP5（rs41494349，rs2306862）处于强LD（D\'>0.9，r2>0.3）。AC和AT单倍型在ABM组中的分布频率明显高于对照组，表明携带AC和AT单倍型的受试者与ABM风险增加相关(P<0.01)。（4）MDR表明rs41494349和rs2302685和rs10743980和年龄是ABM预测的最佳模型。“高风险组合”中ABM的风险是“低风险组合”的1.00倍（OR=1.005，95CI：1.002-1.008，P<0.05）。（5）MDR显示，任何SNPs与绝经年限和ABM易感性之间都没有显着关联。
结论：这些研究结果表明，LRP5-rs2306862和LRP6-rs2302685多态性以及基因-基因和基因-年龄相互作用可能会增加绝经后妇女患ABM的风险。SNP与绝经年限和ABM易感性之间没有显着关联。
方法：本研究根据骨密度（BMD）结果招募了166例ABM患者（病例组）和106例骨量正常的患者（对照组）。多因素降维（MDR）用于分析低密度脂蛋白受体相关蛋白5（LRP5）基因（rs41494349，rs2306862）和低密度脂蛋白受体相关蛋白6（LRP6）基因（rs10743980，rs2302685）与受试者年龄和绝经年龄的临床特征之间的相互作用。
结果：（1）Logistic回归分析显示，rs2306862为CT或TT基因型的受试者患ABM的风险高于CC基因型的受试者（OR=2.353，95CI=1.039-6.186；OR=2.434，95CI=1.071，5.531；P<0.05）。TC基因型rs2302685的受试者发生ABM的风险高于TT基因型（OR=2.951，95CI=1.030-8.457，P<0.05）。（2）当三个单核苷酸多态性（SNP）一起服用时，交叉验证一致性为10/10(OR=1.504,95CI:1.092-2.073,P<0.05),表明LRP5rs41494349和LRP6rs10743980，rs2302685与ABM风险相互作用相关。（3）连锁不平衡（LD）结果表明，LRP5（rs41494349，rs2306862）处于强LD（D\'>0.9，r2>0.3）。AC和AT单倍型在ABM组中的分布频率明显高于对照组，表明携带AC和AT单倍型的受试者与ABM风险增加相关(P<0.01)。（4）MDR表明rs41494349和rs2302685和rs10743980和年龄是ABM预测的最佳模型。“高风险组合”中ABM的风险是“低风险组合”的1.00倍（OR=1.005，95CI：1.002-1.008，P<0.05）。（5）MDR显示，任何SNPs与绝经年限和ABM易感性之间都没有显着关联。
结论：这些研究结果表明，LRP5-rs2306862和LRP6-rs2302685多态性以及基因-基因和基因-年龄相互作用可能会增加绝经后妇女患ABM的风险。SNP与绝经年限和ABM易感性之间没有显着关联。
