Research Foundation, Hospital Clínico Universitario, Av. Blasco Ibáñez, 17, 46010 Valencia, Spain.
Osteoporos Int. 2011 May;22(5):1451-8. doi: 10.1007/s00198-010-1324-0. Epub 2010 Jun 25.
We have analysed the association of single-nucleotide polymorphisms (SNPs) in CD40 and CD40L genes with bone mineral density (BMD) in our women. Results showed that women with TT genotype for rs1883832 (CD40) and for rs1126535 (CD40L) SNPs displayed reduced BMD and increased risk for osteopenia/osteoporosis. Our data notwithstanding, the results need to be replicated.
Recent data have revealed that the CD40/CD40L system can be implicated in bone metabolism regulation. Moreover, we previously demonstrated that rs1883832 in the CD40 gene was significantly associated with BMD and osteoporosis risk. The objective of the present work was to determine whether polymorphisms in CD40 and CD40L genes are associated with BMD and osteoporosis risk.
We conducted an association study of BMD values with SNPs in CD40 and CD40L genes in a population of 811 women of which 693 and 711 had femoral neck (FN) and lumbar spine (LS) densitometric studies, respectively.
Women with the TT genotype for rs1883832 (CD40) showed a reduction in FN-BMD (P = 0.005) and LS-BMD (P = 0.020) when compared with women with the CC/CT genotype. Moreover, we found that rs1126535 (CD40L) was significantly associated with LS-BMD so that women with the TT genotype displayed lower BMD (P = 0.014) than did women with the CC/CT genotype. Interestingly, we have found a strong interaction between polymorphisms in these genes. Thus, women with the TT genotype for both rs1883832 and rs1126535 SNPs (TT + TT women) showed a lower age-adjusted BMD (Z-score) for FN (P = 0.0007) and LS (0.007) after adjusting by years since menopause, body mass index, smoking and menopausal status, densitometer type, hormone replacement therapy (HRT) use and HRT duration and after making the Bonferroni adjustment for multiple comparisons than did the remaining women. Logistic regression analysis adjusted by these covariates showed that TT + TT women had increased risk for FN (odds ratio (OR) = 2.76; P = 0.006) and LS (OR = 2.39; P = 0.020) osteopenia or osteoporosis than did the other women.
Our results suggest that interaction between genetic variants in the CD40 and CD40L genes exerts a role on BMD regulation. Further studies, which we welcome, are needed to replicate these data in other populations.
我们分析了 CD40 和 CD40L 基因中的单核苷酸多态性（SNPs）与女性骨密度（BMD）之间的关联。结果表明，rs1883832（CD40）和 rs1126535（CD40L）SNP 的 TT 基因型女性的 BMD 降低，骨质疏松症/骨质疏松症风险增加。尽管我们的数据表明，这些结果需要复制。
最近的数据表明，CD40/CD40L 系统可能与骨代谢调节有关。此外，我们之前的研究表明，CD40 基因中的 rs1883832 与 BMD 和骨质疏松症风险显著相关。本研究的目的是确定 CD40 和 CD40L 基因中的多态性是否与 BMD 和骨质疏松症风险相关。
我们对 811 名女性的 CD40 和 CD40L 基因中的 SNPs 与 BMD 值进行了关联研究，其中 693 名和 711 名女性分别进行了股骨颈（FN）和腰椎（LS）骨密度测量。
与 CC/CT 基因型女性相比，rs1883832（CD40）的 TT 基因型女性 FN-BMD（P=0.005）和 LS-BMD（P=0.020）降低。此外，我们发现 rs1126535（CD40L）与 LS-BMD 显著相关，因此 TT 基因型女性的 BMD 低于 CC/CT 基因型女性（P=0.014）。有趣的是，我们发现这些基因中的多态性之间存在强烈的相互作用。因此，rs1883832 和 rs1126535 两个 SNP 的 TT 基因型女性（TT+TT 女性）的 FN（P=0.0007）和 LS（0.007）的年龄调整后的 BMD（Z 评分）较低，调整了绝经后年限、体重指数、吸烟和绝经状态、骨密度仪类型、激素替代疗法（HRT）使用情况和 HRT 持续时间后，经 Bonferroni 多重比较校正后，这些女性的 BMD 明显低于其他女性。经过这些协变量调整的逻辑回归分析显示，TT+TT 女性 FN（优势比（OR）=2.76；P=0.006）和 LS（OR=2.39；P=0.020）骨质疏松症或骨质疏松症的风险增加。
我们的结果表明，CD40 和 CD40L 基因中的遗传变异之间的相互作用对 BMD 调节起作用。需要进行进一步的研究来复制这些数据在其他人群中的结果。
