COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women

Abstract

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.

Methods: A case–control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy–Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.

Results: COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.

Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

摘要

目的：本研究目的是分析一组绝经后的墨西哥女性五个ESR1单核苷酸多态性（SNP）（rs3020331, rs851982, rs1999805, rs2234693, rs3020404）, 四个COL1A1 SNP（rs1800012, rs2075555, rs2412298, rs1107946）和两个CCDC170基因的SNP（rs9479055, rs4870044）与桡骨远端骨折（DRF）的遗传关联性研究。

方法：进行病例对照研究。病例（n = 182）是38岁以上低能量DRF的女性, 对照组（n = 201）是无骨折的女性。通过实时聚合酶链反应进行分析。计算频率和Hardy-Weinberg平衡。进行了多因素分析, 包括骨质量指数, 年龄, 初潮和绝经年龄作为协变量。最后, 进行了单倍体和连锁不平衡（LD）分析。

结果：COL1A1 rs1107946与DRF密切相关。两种CCDC170 SNP均与DRF密切相关。对于ESR1基因, 四个SNP（rs2234693、3020404, rs3020331和rs851982）显示出与DRF的紧密关联。另外, 后两者之间的区域显示出较强的LD。

结论：发现DRF与这些基因的变异密切相关, 包括单倍型和ESR1上具有强LD的区域。结果表明, 这些SNP可用于检测墨西哥围绝经期妇女存在DRF风险的人群。

Keywords:

• Bone mineral density
• polymorphisms
• ESR1
• COL1A1
• CCDC170
• distal radius fracture

Acknowledgements

The authors want to thank the support from the staff of the Laboratory of Genetics – National Institute of Rehabilitation, specially Blanca Alicia Barredo-Prieto QFB, Edith Falcón-Ramírez PhD, and Valeria Ponce de León-Suárez PhD. Also, staff from the Hand Surgery and Microsurgery Division, especially Head of Division Alejandro Espinosa-Gutiérrez, MD and Head Nurse Sandra Ramírez-Velázquez, RN.

Potential conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work received financial support from the National Institute of Rehabilitation. Dr Farias-Cisneros was supported by the National Council of Science and Technology – Mexico (CONACYT) [grant number 269915].