University Medical Centre Ljubljana, Institute of Clinical Chemistry and Biochemistry, Ljubljana, Slovenia.
Dis Markers. 2010;29(2):71-80. doi: 10.3233/DMA-2010-0728.
Recently, oxidative stress has been suggested as participating in the development of osteoporosis. Glutathione peroxidase 1 (GPX1) is one of antioxidant enzymes responsible for the defence of cells against oxidative damage and thus for protection against age related diseases such as osteoporosis. The aim of present study was to associate genetic variances of GPX1 enzyme with bone mineral density (BMD) and biochemical bone turnover markers and to show the influence of antioxidative defence system in genetics of osteoporosis. We evaluated 682 Slovenian subjects: 571 elderly women and 111 elderly men. All subjects were genotyped for the presence of GPX1 gene polymorphisms Pro198Leu and polyAla region. BMD and biochemical markers were also measured. General linear model analysis, adjusted to height, and (one-way) analysis of variance were used to assess differences between the genotype.and haplotype subgroups, respectively. The significant or borderline significant associations were found between the polyAla or the Pro198Leu polymorphisms and total hip BMD (0.018; 0.023, respectively), femoral neck BMD (0.117; 0.026, respectively) and lumbar spine BMD (0.032; 0.086, respectively), and with biochemical bone turnover markers such as plasma osteocalcin (0.027; 0.025, respectively) and serum C-terminal telopeptide of type I collagen concentrations (0.114; 0.012, respectively) in whole group. Haplotype analysis revealed that the 6-T haplotype is associated significantly with low BMD values (p< 0.025) at all measured locations of the skeleton, and with high plasma osteocalcin concentrations (p=0.008). This study shows for the first time that the polymorphisms polyAla and Pro198Leu of the GPX1 gene, individually and in combination, are associated with BMD and therefore may be useful as genetic markers for bone disease. Moreover, it implies the important contribution of the oxidative stress to pathogenesis of osteoporosis.
最近，氧化应激被认为参与了骨质疏松症的发生。谷胱甘肽过氧化物酶 1 (GPX1) 是一种抗氧化酶，负责保护细胞免受氧化损伤，从而预防与年龄相关的疾病，如骨质疏松症。本研究的目的是将 GPX1 酶的遗传变异与骨密度 (BMD) 和生化骨转换标志物相关联，并展示抗氧化防御系统在骨质疏松症遗传学中的影响。我们评估了 682 名斯洛文尼亚受试者：571 名老年女性和 111 名老年男性。所有受试者均进行了 GPX1 基因多态性 Pro198Leu 和多聚 Ala 区的基因型分析。还测量了 BMD 和生化标志物。使用一般线性模型分析，调整身高，并（单向）方差分析分别评估基因型和单倍型亚组之间的差异。多聚 Ala 或 Pro198Leu 多态性与总髋部 BMD（0.018；0.023）、股骨颈 BMD（0.117；0.026）和腰椎 BMD（0.032；0.086）之间存在显著或边缘显著的关联，与生化骨转换标志物如血浆骨钙素（0.027；0.025）和血清 I 型胶原 C 末端肽浓度（0.114；0.012）之间存在显著或边缘显著的关联。整个研究组。单体型分析表明，6-T 单体型与所有骨骼测量部位的低 BMD 值显著相关（p<0.025），与高血浆骨钙素浓度相关（p=0.008）。这项研究首次表明，GPX1 基因的多态性 polyAla 和 Pro198Leu 单独和组合与 BMD 相关，因此可能是骨疾病的有用遗传标志物。此外，它暗示氧化应激对骨质疏松症发病机制的重要贡献。
