An SP1-binding site polymorphism in the COLIAI gene and osteoporosis in Egyptian patients with thalassemia major

Abstract

β-Thalassemia major is an inherited blood disorder, which mainly affects the Mediterranean region. Osteoporosis represents an important cause of morbidity in β-thalassemia major and its pathogenesis has not been completely clarified. Genetic factors play an important role in the pathogenesis of osteoporosis and several candidate gene polymorphisms have been implicated in the regulation of this process. A G→T polymorphism in the regulatory region of the collagen type I alpha 1 (COLIAI) gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporosis. The aim of the present study was to examine the distribution of COLIAI polymorphism and its relationship with bone mineral density (BMD) at the lumbar spine and femur in patients and controls. In this study, the G→T polymorphism was detected in 31 Egyptian β-thalassemia major patients and 20 healthy controls and its possible association with BMD was investigated. Alleles S and s were detected by the presence of a G or T nucleotide, respectively, in a regulatory site of the COLIAI gene using polymerase chain reaction (PCR). A total of 80.6% of the β-thalassemia patients were homozygous for G/G (SS) and 19.4% were heterozygotes for G/T (Ss) polymorphism. There was no ss genotype in our patients. In the control group, 70 and 30% had SS and Ss genotypes, respectively. There was no significant difference between Z-score of patients with SS and Ss at head of femur (P = 1) or at lumbar spine (P = 0.48). Conclusion Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying the thalassemic patients at risk of developing osteoporosis.

The Evaluation of Bone Mineral Density in Patients with Thalassemia Major

“…It is characterized by reduced bone mass, disruption of bone architecture, and increased risk of bone fragility and fractures [4,11,13]. Bone loss is a common feature even in well-treated thalassemia patients and despite adequate transfusion and iron chelation.…”

Endocrinopathies in Hemoglobinopathies: What Is the Role of Iron?

“…Rs4701 variant in the VDBP gene, which encodes vitamin D binding protein, has been associated with lower BMD in β-thalassemia patients, as shown in a case-control study [157]. The presence of a polymorphism at the Sp1 binding site of the collagen type I A1 (COLIA1) gene (G > T, at first intron) is considered to be a major factor in the development of low BMD and osteoporosis in both patients with β-thalassemia and in the general population [158][159][160]. FokI and BsmI polymorphisms at the Vitamin D receptor (VDR) gene have been correlated with low BMD and increased risk of osteoporosis in several studies [161][162][163][164][165].…”

Osteoporosis in Thalassemia Major

“…The polymorphism at the Sp1 site of the COLIA 1 gene has been associated with severe osteoporosis and pathologic fractures of the spine and the hip in TM patients. Early detection of this mutation is important to start the treatment before fractures occur (7,13,14). The vitamin D receptor (VDR) polymorphism is also a risk factor for bone mineral damage and low bone mineral density (BMD) (8,13).…”

“…Osteoporosis is the most common involvement of the skeletal system and represents an important cause of morbidity in adult patients (2,(4)(5)(6). It is characterized by reduced bone mass, disruption of bone architecture and increased risk of bone fragility and fractures (4,7,8). In this review, we present an overview of osteoporosis and its treatment modalities in patients with TM.…”