Investigation of PvuII polymorphism of estrogen receptor alpha (ERα) gene in patients with osteoporosis in Bushehr elderly health study
In 1993, the WHO defined osteoporosis as a systemic skeletal disease characterized by low bone mass, impaired bone structure and function, and consequent increased bone fragility and increased risk of fracture. In addition, it has been reported that osteoporosis occurs when there is an imbalance in bone cell function. The disease has been called the “silent epidemic of the 21st century” due to its consequences on public health. Osteoporosis is a severe, chronic, progressive, and the most common metabolic bone disease. Among the metabolic bone diseases known to date, osteoporosis is not only the most common bone disorder but also a major global public health problem due to its high morbidity, which is caused by osteoporotic fractures in the elderly population. This process occurs in both sexes and in various types of osteoporosis and is known to affect both children and young patients, either primary or secondary to systemic diseases or medical treatments. Given that bone loss occurs with age, the prevalence of osteoporosis also increases with age. Therefore, as a chronic and long-term skeletal disorder, osteoporosis is more common in older people, occurring in approximately 100% of men over 65 years of age and in approximately 100% of women over 55 years of age.
Many genetic and environmental factors contribute to the development of osteoporosis. Genes that contribute to bone metabolism include calcium-regulating hormone receptors such as estrogen receptor (ESR1)α, cytokines and other bone-related proteins. Estrogens maintain various biological processes such as normal cell proliferation and differentiation, development and regulation of tissue-related genes through binding to ESR1 and ESR2 receptors. Following this binding, a conformational change occurs in the receptors, leading to interaction with specific high-affinity DNA sequences (ERE) in the promoter regions of target genes that regulate transcriptional processes. Human ESR1 is expressed in a variety of cell types, including osteoblasts, osteoclasts, and chondrocytes, which may indicate that bone and cartilage are targets of estrogens. Also, mutations in ESR1 are associated with changes in bone mass and delayed skeletal growth. Two common polymorphisms in intron 1 of ESR1 are known as PvuII and XbaI. As mentioned, estrogen receptor alpha (ERα) plays an important role in the regulation of bone metabolism, and genetic variations in the ERα gene are implicated in the pathogenesis of osteoporosis. One of the polymorphisms of this gene is the PvuII polymorphism, which is associated with altered expression and function of the ERα gene. However, the association between the PvuII polymorphism of the ERα gene and osteoporosis in Iranian patients has not been extensively studied.
This research can help identify genetic factors in early diagnosis and prevention of this disease and help develop more targeted treatment methods. Therefore, a deeper investigation of this polymorphism in Iranian osteoporosis patients will not only help to better understand the biological processes of this disease but may also be effective in implementing preventive methods and developing more effective treatment methods at the national level.
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