Kim Su Kang, Hong Seoung-Jin, Kim Gyutae, Ban Ju Yeon, Kang Sang Wook
Department of Biomedical Laboratory Science, Catholic Kwandong University, Gangneung 25601, Republic of Korea.
Department of Prosthodontics, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2025 Aug 22;26(17):8177. doi: 10.3390/ijms26178177.
Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis ( < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency ( < 0.01). Several of these genes were implicated in bone metabolism (e.g., , , ), vitamin D metabolism (e.g., , ), skeletal muscle function (e.g., , ), and reproductive processes (e.g., , , ). Notably, the rs783540 SNP exhibited the strongest association ( < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle-bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms.
骨质疏松症是一种常见疾病，其特征是骨矿物质密度（BMD）降低，导致病理性骨折风险增加，甚至死亡。虽然绝经是一个主要危险因素，但骨质疏松症也可发生在绝经前女性中。本研究的目的是确定与韩国绝经前女性骨质疏松症发生相关的基因变异。研究对象来自韩国基因组与流行病学研究（KoGES）的安城和安山队列。评估了临床和流行病学特征，并根据桡骨远端和胫骨中段测量的BMD值对参与者进行分类。排除了体重过低、吸烟、高酒精摄入、类固醇/激素治疗或相关病史等混杂危险因素的个体。共纳入247名健康对照者和57名骨质疏松症患者。使用Illumina Infinium HumanExome BeadChip和Affymetrix Axiom Exome Array进行基因分型。使用SNP和变异套件以及PLINK分析数据，质量控制阈值设定为MAF≥0.05和HWE≥0.01。使用PolyPhen-2、SIFT和PROVEAN进行功能注释和蛋白质结构预测。全基因组关联分析在两个平台上均鉴定出69个基因中的113个单核苷酸多态性（SNP）与骨质疏松症显著相关（P<0.05），其中18个SNP显示出高跨平台一致性（P<0.01）。这些基因中的几个与骨代谢（如……）、维生素D代谢（如……）、骨骼肌功能（如……）和生殖过程（如……）有关。值得注意的是，rs783540 SNP在两项分析中均表现出最强的关联（P<0.001）。我们的研究结果表明，与骨代谢、维生素D信号传导、肌肉-骨相互作用和生殖激素调节相关途径中的基因多态性可能有助于韩国绝经前女性骨质疏松症的发生。这些结果为早期识别高危个体提供了遗传基础，并值得进一步开展功能研究以阐明潜在机制。
