Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women

Abstract

Aims

Osteoporosis (OP) remains a major public health problem worldwide. The most serious complications of this disease are fragility fractures, which increase morbidity and mortality. Management of OP represents an economic burden for health systems. Therefore, it is necessary to develop new screening strategies to identify the population at risk and implement preventive measures. We previously identified the SNPs rs3801387 in WNT16, rs7108738 in SOX6, rs10036727 in SLIT3 and rs7584262 in PKDCC as associated with bone mineral density in postmenopausal women through a genome-wide association study. The aim of this study was to validate those SNPs in two independent cohorts of non-related postmenopausal women.

Materials and methods

We included 1160 women classifying them as normal, osteopenic or osteoporotic and a group with hip fragility fracture. Genotyping was performed using predesigned TaqMan assays.

Results

The variants rs10036727 and rs7108738 showed a significant association with BMD at the femoral neck. SLIT3 has been previously proposed as a potential biomarker and therapeutic resource.

Conclusions

Our results provide new evidence regarding a possible involvement of SLIT3 in bone metabolisms and encourage the development of more studies in different populations to support these observations.

摘要

目的：骨质疏松症（OP）仍然是世界范围内的一个主要公共卫生问题。这种疾病最严重的并发症是脆性骨折, 增加了女性的发病率和死亡率。OP的管理对卫生系统来说是一种经济负担。因此有必要制定新的筛查策略, 以识别高危人群并实施预防措施。我们先前通过全基因组关联研究发现WNT16中的rs3801387、SOX6中的rs7108738、SLIT3中的rs10036727和PKDCC中的rs7584262与绝经后女性的骨密度相关。这项研究的目的是在两个独立的无血缘关系的绝经后女性队列中验证这些SNPs。

材料和方法：我们将1160名女性分为正常组、骨质疏松症或骨质疏松组和髋关节脆性骨折组。采用预先设计的TaqMan方法进行基因分型。

结果：rs10036727和rs7108738变异与股骨颈骨密度显著相关。SLIT3被认为是一种潜在的生物学标志物和治疗资源。

结论：我们的研究为SLIT3可能参与骨代谢提供了新的证据, 并鼓励在不同人群中开展更多的研究来支持这一结论。

Keywords:

• Osteoporosis
• bone mineral
• density genetic association
• biomarkers
• fragility fracture

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the INMEGEN [64-18/2011/I] and received partial funding from CONACYT under grants: INFR-2016-01-270405 and CB-2013–1-221628.