The Study of G/T Polymorphism in COLIA1 Gene and Osteoporosis in b-Thalassemia Patients.

Osteoporosis is an important cause of morbidity in patients with β thalassemia major. Several genes are thought to be involved in the pathogenesis of osteoporosis. Collagen type I alpha 1 (COLIA1) is one of the most prominent candidate genes, which has been consistently associated with osteoporosis in different populations. Polymorphism at the Sp1 binding site within a key regulatory region of COLIA 1 has been reported to be associated with susceptibility to osteoprotic fractures. Our objective was to detect the allelic distribution of COLIA1 gene in beta thalassemia patients and its relation to bone mineral density (BMD).

The study included 25 beta thalassemia major patients (12-28 years, mean = 18.12±5.077 years) and 20 controls (mean age = 23.05±2.3 years) with no family history of thalassemia. Anthropometric measurements were done to all patients .Femoral and lumbar BMD was measured in all patients and control groups using dual energy absorbiometry (DXA). Assessment of the COLIA1 genotypes (SS, Ss, ss) and G/T polymorphism were done using PCR amplification and restriction enzyme digestion (Bal1) of DNA amplified products to thalassemic patients and control groups.

High prevalence of growth retardation was observed in β thalassemia major patients in the form of short stature (36%), truncal shortening (48%) and under weight (8%). Osteopenia and osteoporosis were detected in 68% of the thalassemia patients with a highly significant lower lumbar and femoral BMD compared to controls (P<0.01) (Table 1). There was a non significant difference between genders regarding BMD, significant negative correlation was observed between long duration of desferroxamine (DFO) intake and low femoral and lumbar BMD (R=-0.571& P<0.01,R=-0.571&P<0.05) in β thalassemia patients. A negative correlation was observed between ferritin level and fat free mass% (FFM%) in thalassemic patients (R=-0.48& P<0.05) and low lumbar BMD in female patients (R=-0.55& P<0.05). There was a positive correlation between age of starting DFO and decreased sitting height in male patients (R=0.74&P<0.01). In the thalassemic group, frequency of COLIA1 alleles was S (94%), s (6%), 12% showed the G/T polymorphism while 88% had the G/G polymorphism (Table 2). Non significant difference was observed in most of the parameters between the 2 different groups of polymorphism. In the control group allele frequencies were S (87.5%) and s (12.5%), G/T polymorphism was present in 25%.and G/G in 75%. No association was detected between COLIA1 gene polymorphism and BMD in the lumbar spine or in femur bone in the thalassemia patients (P>0.05) while the s allele was associated with femoral and lumbar BMD in the control group (P<0.05, P<0.01) (Table 3).

High prevalence of growth impairment, osteopenia and osteoporosis in our β thalassemia major patients. Desferroxamine duration therapy was related to osteoporosis in our patients. The absence of association between BMD and COLIA 1 polymorphism and the low frequency of s allele in our thalassemic group may be due to the small sample size of the thalassemia patients together with the fact that BMD is determined by a variety of genetic and environmental factors. Further studies including larger number of patients are needed to evaluate these findings.

No relevant conflicts of interest to declare.