Effect of VDR polymorphisms on growth and bone mineral density in homozygous beta thalassaemia.

We examined the effect of vitamin D receptor (VDR) polymorphisms at exon 2 (FokI) and intron 8 (BsmI) on the stature and bone mineral density at femoral neck (FBMD) and lumbar spine (LBMD) in 108 prepubertal and pubertal homozygous beta thalassaemic patients, regularly treated. We found significantly shorter stature and lower LBMD and FBMD in all patients with CC VDR genotype, and significant shorter height and lower LBMD in prepubertal and pubertal female patients with BB VDR genotype. Because homozygous CC and BB VDR genotypes influence Vitamin D activity, they can be considered additional risk factors for bone disease in beta thalassaemia.

Cardiac involvement in beta-thalassemia major and beta-thalassemia intermedia.

The forms and severity of cardiac complications were investigated in patients with asymptomatic thalassemia intermedia and thalassemia major by M-mode, bi-dimensional echocardiography (ECHO) and echo-Doppler. Twenty-eight patients of both sexes with beta-thalassemia intermedia (beta-TI), mean age 23.2 +/- 6.3 years, untransfused or minimally transfused, were compared to 42 age- and sex-matched subjects with thalassemia major, who were regularly treated with hemotransfusive therapy [pre-transfusion hemoglobin (Hb) values 9.5 +/- 0.9 g/dL] and iron chelation. All patients were splenectomized. Age and sex matched healthy control subjects were randomly selected. beta-Thalassemia major (beta-TM) patients showed a marked reduction in contractile state and a milder left ventricular (LV) enlargement than beta-TI patients. Cardiac output (CO) and cardiac index (CI) were increased in both groups of patients but appeared significantly higher in beta-TI patients with consequent altered LV diastolic function indices. In addition, beta-TI patients had reduced indices of pulmonary artery flow related to long-term chronic anemia rather than iron overload. The progressive rise in CO and CI casts doubts on the current management of beta-TI syndromes.

Role of polymorphic sequences 5' to the G(gamma) gene and 5' to the beta gene on the homozygous beta thalassemic phenotype.

Sixty-seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their beta-thalassemia (thal) mutations. We investigated whether some co-inherited genetic factors could influence the phenotype. Patients with milder beta-thal defects, homozygotes or compound heterozygotes for the IVS-I-6 (T-->C) or -87 (C-->G) mutations had a milder disease. In addition, determination of the co-inheritance of the -158 (C-->T) G(gamma) polymorphism and the (AT)9T5 repeat motif in the region -540 to -525, 5' to the beta-globin gene, showed that in some patients with severe or mild/severe beta-thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous beta-thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the -158 (C-->T) G(gamma) and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.