Department of Orthopedics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, PR China.
Department of Orthopedics, the Second Affiliated Hospital of Wenzhou, Medical University, Zhejiang, PR China.
Biosci Rep. 2019 Jan 18;39(1). doi: 10.1042/BSR20181505. Print 2019 Jan 31.
The aim of the present study was to investigate the associations between single nucleotide polymorphisms (SNPs) in the PDZ and LIM domain protein 4 () gene and susceptibility to osteoporotic fracture in an elderly Han Chinese population. Seven SNPs of , including rs77584624, rs78418541, rs270611, rs3900945, rs77486529, rs71583465, and rs366512, were examined in 540 elderly Chinese patients with osteoporotic fractures (case group) and 540 healthy Chinese subjects (control group) using Sanger sequencing. A-allele carriers of rs270611 in PDLIM4 had a significantly high risk of osteoporotic fracture (adjusted odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.24-1.46; <0.001). Similarly, individuals carrying the C-allele at PDLIM4 rs3900945 were predisposed to osteoporotic fracture (adjusted OR = 1.45; 95% CI: 1.05-1.25; <0.001). In contrast, the T-allele at rs366512 appeared to be a protective genetic factor against osteoporotic fracture (adjusted OR = 0.84; 95% CI: 0.74-0.95; <0.01). Consistently, the serum levels of N-terminal propeptide of type I procollagen (PINP) and C-telopeptide fragments of Collagen type I α1 chains (β-CTx) were higher in A-allele carriers of rs270611 and C-allele carriers of rs3900945, while T-allele carriers of rs366512 had lower PINP and β-CTx levels. Corresponding well with published findings, the A-allele of rs270611 and C-allele of rs3900945 were associated with reduced bone marrow density (BMD) at the fracture site, while T-allele carriers of rs366512 were shown to have normal BMD. Our study provides supportive evidence for the contribution of gene polymorphisms to the susceptibility to osteoporotic fracture and suggests that rs270611 and rs3900945 are genetic risk factors, while rs366512 might be a genetic protective factor against osteoporotic fracture in elderly Han individuals.
本研究旨在探讨 PDZ 和 LIM 域蛋白 4 () 基因中的单核苷酸多态性 (SNP) 与老年汉族人群骨质疏松性骨折易感性之间的关系。对 540 例骨质疏松性骨折老年患者（病例组）和 540 例健康中国受试者（对照组）进行了 7 个 SNP(rs77584624、rs78418541、rs270611、rs3900945、rs77486529、rs71583465 和 rs366512)的 Sanger 测序分析。在 PDLIM4 中 rs270611 的 A 等位基因携带者发生骨质疏松性骨折的风险显著升高(校正优势比[OR]=1.34;95%置信区间[CI]:1.24-1.46;<0.001)。同样，在 PDLIM4 rs3900945 中携带 C 等位基因的个体易患骨质疏松性骨折(校正 OR=1.45;95%CI:1.05-1.25;<0.001)。相反，rs366512 的 T 等位基因似乎是骨质疏松性骨折的保护性遗传因素(校正 OR=0.84;95%CI:0.74-0.95;<0.01)。一致的是，在 rs270611 的 A 等位基因携带者和 rs3900945 的 C 等位基因携带者中，I 型前胶原 N 端前肽(PINP)和 I 型胶原α1 链 C 端肽片段(β-CTX)的血清水平升高，而 rs366512 的 T 等位基因携带者的 PINP 和 β-CTX 水平较低。与已发表的研究结果一致，rs270611 的 A 等位基因和 rs3900945 的 C 等位基因与骨折部位的骨髓密度(BMD)降低相关，而 rs366512 的 T 等位基因携带者的 BMD 正常。本研究为 基因多态性与骨质疏松性骨折易感性的关系提供了支持性证据，并表明 rs270611 和 rs3900945 是遗传危险因素，而 rs366512 可能是汉族老年人骨质疏松性骨折的遗传保护因素。
