Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India.
Division of Statistical Quality Control and Operations Research, Indian Statistical Institute, Pune, Maharashtra, India.
Indian J Med Res. 2022 Oct-Nov;156(4&5):640-647. doi: 10.4103/ijmr.IJMR_208_20.
BACKGROUND & OBJECTIVES: Osteoporosis is a systemic skeletal disease, characterized by a low bone mass leading to increased bone fragility and hence, a greater susceptibility to the risk of fracture. Since age-related oxidative stress is one of the factors that has been implicated in developing low bone mineral density (BMD), leading to osteoporosis, this study wanted to explore the expression of antioxidant enzymes in individuals with osteoporosis. The present study focused on mapping polymorphism in an important antioxidant enzyme glutathione peroxidase 1 (GPx1) among osteoporosis and healthy Asian Indians.
Dual-energy X-ray absorptiometry was used to assess BMD of individuals and was classified into normal (n=96) and osteoporotic (n=88) groups. Biochemical parameters such as vitamin D, total oxidant status (TOS), and GPx1 enzyme activity were estimated from plasma samples of recruited individuals. Quantitative real-time qRT-PCR was carried out using GAPDH as an endogenous control. Genomic DNA was isolated from whole blood, and polymorphisms were evaluated by sequencing.
The BMD was lower in osteoporotic individuals, and further analysis of biochemical parameters indicated significantly low 25-hydroxy vitamin D and GPx1 with higher TOS levels in osteoporotic as compared to healthy individuals. Furthermore, qRT-PCR revealed low expression of GPX1 in osteoporotic individuals. GPX1 sequence analysis of the promoter and two exons revealed the lower frequency of five alanine repeats in the osteoporotic individuals.
INTERPRETATION & CONCLUSIONS: In this study, the in silico analysis revealed the lower frequency of five alanine repeats in exon 1 of GPX1 and high TOS to be associated with osteoporosis. However, no polymorphism was found in exon 2 of GPX1 among the two study groups.
骨质疏松症是一种全身性骨骼疾病,其特征是骨量低,导致骨脆性增加,从而更容易发生骨折风险。由于与年龄相关的氧化应激是导致低骨密度(BMD)从而导致骨质疏松症的因素之一,因此本研究旨在探讨骨质疏松症个体中抗氧化酶的表达。本研究主要集中在研究重要抗氧化酶谷胱甘肽过氧化物酶 1(GPx1)在骨质疏松症和健康亚洲印度人中的多态性。
双能 X 射线吸收法用于评估个体的 BMD,并将其分为正常(n=96)和骨质疏松(n=88)组。从招募个体的血浆样本中估计生化参数,如维生素 D、总氧化状态(TOS)和 GPx1 酶活性。使用 GAPDH 作为内参进行定量实时 qRT-PCR。从全血中分离基因组 DNA,并通过测序评估多态性。
骨质疏松症个体的 BMD 较低,进一步分析生化参数表明,与健康个体相比,骨质疏松症个体的 25-羟维生素 D 和 GPx1 明显较低,而 TOS 水平较高。此外,qRT-PCR 显示骨质疏松症个体的 GPX1 表达较低。GPX1 启动子和两个外显子的序列分析显示,骨质疏松症个体中五个丙氨酸重复的频率较低。
在这项研究中,计算机分析显示 GPX1 外显子 1 中的五个丙氨酸重复频率较低和 TOS 较高与骨质疏松症有关。然而,在两个研究组中,GPX1 外显子 2 中没有发现多态性。