Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People's Republic of China.
Calcif Tissue Int. 2023 Aug;113(2):207-215. doi: 10.1007/s00223-023-01102-2. Epub 2023 Jul 4.
Recent studies have discovered an association between the PFN1 gene and Paget's disease. However, it is currently unknown whether the PFN1 gene is related to osteoporosis. This study was performed to investigate the association of Single-Nucleotide Polymorphisms (SNPs) in the PFN1 gene with Bone Mineral Density (BMD) as well as bone turnover markers and osteoporotic fractures in Chinese subjects. A total of 2836 unrelated Chinese subjects comprising 1247 healthy subjects and 1589 osteoporotic fractures patients (Fracture group) were enrolled in this study. Seven tagSNPs (rs117337116, rs238243, rs6559, rs238242, rs78224458, rs4790714, and rs13204) of the PFN1 gene were genotyped. The BMD of the lumbar spine 1-4 (L1-4), femoral neck, and total hip as well as bone turnover markers, such as β-C-Terminal telopeptide of type 1 collagen (β-CTX) and Procollagen type 1 N-terminal Propeptide (P1NP), were measured. The association between 7 tagSNPs and BMD and bone turnover markers was analyzed in 1247 healthy subjects only. After age matching, we selected 1589 osteoporotic fracture patients (Fracture group) and 756 nonfracture controls (Control group, selected from 1247 healthy subjects) for a case-control study, respectively. For the case-control study, we used logistic regression to investigate the relationship between 7 tagSNPs and osteoporotic fractures risk. In the All group, the PFN1 haplotype GAT was associated with the β-CTX (P = 0.007). In the Female group, the PFN1 haplotype GAT was associated with the β-CTX (P = 0.005). In the Male group, the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the L1-4 (all P = 0.012); the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the femoral neck (all P = 0.012); the rs13204 and rs78224458 were associated with the BMD of the total hip (both P = 0.015); and the PFN1 haplotype GAT was associated with the β-CTX (P = 0.013). In the subsequent case-control study, the rs13204 and rs78224458 in the male group were associated with the risk of L1-4 fracture (P = 0.016 and 0.010, respectively) and total hip fracture (P = 0.013 and 0.016, respectively). Our study reveals that PFN1 gene polymorphisms are associated with BMD in Chinese males and β-CTX in Chinese people and confirmed the relationship between PFN1 gene polymorphisms and Chinese male osteoporotic fractures in a case-control study.
最近的研究发现，PFN1 基因与 Pagets 病之间存在关联。然而，目前尚不清楚 PFN1 基因是否与骨质疏松症有关。本研究旨在探讨中国人群中 PFN1 基因单核苷酸多态性（SNP）与骨密度（BMD）以及骨转换标志物和骨质疏松性骨折之间的关系。本研究共纳入了 2836 名无血缘关系的中国受试者，包括 1247 名健康受试者和 1589 名骨质疏松性骨折患者（骨折组）。对 PFN1 基因的 7 个标签 SNP（rs117337116、rs238243、rs6559、rs238242、rs78224458、rs4790714 和 rs13204）进行了基因分型。测量了腰椎 1-4（L1-4）、股骨颈和全髋关节的 BMD 以及骨转换标志物，如 1 型胶原 β-C 端肽（β-CTX）和前胶原 1 N 端前肽（P1NP）。仅在 1247 名健康受试者中分析了 7 个标签 SNP 与 BMD 和骨转换标志物之间的关系。在年龄匹配后，我们分别为 1589 名骨质疏松性骨折患者（骨折组）和 756 名非骨折对照（从 1247 名健康受试者中选择）选择了病例对照研究。对于病例对照研究，我们使用 logistic 回归来研究 7 个标签 SNP 与骨质疏松性骨折风险之间的关系。在所有组中，PFN1 单倍型 GAT 与β-CTX 相关（P=0.007）。在女性组中，PFN1 单倍型 GAT 与β-CTX 相关（P=0.005）。在男性组中，rs13204、rs78224458 和 PFN1 单倍型 GAC 与 L1-4 的 BMD 相关（均 P=0.012）；rs13204、rs78224458 和 PFN1 单倍型 GAC 与股骨颈的 BMD 相关（均 P=0.012）；rs13204 和 rs78224458 与全髋关节的 BMD 相关（均 P=0.015）；PFN1 单倍型 GAT 与β-CTX 相关（P=0.013）。在随后的病例对照研究中，男性组中的 rs13204 和 rs78224458 与 L1-4 骨折（P=0.016 和 0.010）和全髋关节骨折（P=0.013 和 0.016）的风险相关。我们的研究表明，PFN1 基因多态性与中国男性的 BMD 和中国人的β-CTX 相关，并在病例对照研究中证实了 PFN1 基因多态性与中国男性骨质疏松性骨折之间的关系。
