Association of RMND1/CCDC170–ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women

Abstract

Objective: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population.

Methods: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association.

Results: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups.

Conclusion: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.

Chinese abstract

目的：本研究旨在研究RMND1、CCDC170和ESR1基因7个单核苷酸多态性（SNPs）与绝经后墨西哥人群骨质疏松症或髋关节骨折的相关性。

方法：我们从墨西哥社会保障研究所的卫生工作者队列研究中纳入400名绝经后妇女, 从国家康复研究所招募了423名绝经后妇女作为复制病例组。通过结构化问卷收集人口统计数据, 采用双能x线骨密度测定法测定骨密度。根据世界卫生组织的标准, 将受试者分为正常组、骨量减少组、骨质疏松组和骨折组。采用预先设计的TaqMan探针进行基因分型, 采用线性回归分析的方法研究相关性。

结果：所有被分析的单核苷酸多态性与研究小组的至少一个表型有关。此外, 我们还观察到所有组的ESR1基因中都存在一个连锁失衡区域。

结论：本研究表明单核苷酸多态性与骨量减少、骨质疏松、脆性骨折等可能存在相关性。我们的结果与已发表的其它数据一致, 支持了这些位点对于识别潜在危险人群的能力。但是, 还需要进行更多的研究, 以确定这种相关性对墨西哥其他地理区域的影响程度。

Keywords:

• Osteoporosis
• single nucleotide polymorphism
• genetic association
• hip fracture
• bone mineral density

Acknowledgements

The authors would like to acknowledge the study participants for their collaboration and the staff from the Unidad de Investigación Epidemiológica y en Servicios de Salud, IMSS, Cuernavaca, Morelos and the staff from the Laboratory of Genetics from the INR.

Conflict of interest

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT) [grant SALUD-2010-C01-139795]; [grant INFR-2016-01-270405]; partially supported by Instituto Nacional de Medicina Genomica [64-18/2011/I]