XmnI polymorphism frequency in heterozygote beta thalassemia subjects and its relation to Fetal hemoglobin levels.

Thalassemias are common monogenic disorders caused by partial or complete reduction synthesis of one or more globin chains.( The normal concentrations of fetal hemoglobin (Hb F) in adults without Hb alterations range from 0% to 1%.( It is known that stimulation of Hb F production is beneficial to homozygous beta-thalassemia individuals( and that the XmnI polymorphism may be related to increases.( The objectives of this study were to evaluate the frequency of the XmnI polymorphism in heterozygous beta-thalassemia subjects and in individuals without Hb alterations, to estimate the polymorphism frequency related with beta thalassemia mutations and to correlate the presence of the XmnI polymorphism with Hb F levels. A total of 325 peripheral blood samples from control (n=169) and beta thalassemia trait individuals (n=156) were submitted to classical tests for hemoglobinopathies.( The presence or absence of the XmnI polymorphism was analyzed in both groups by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).( Statistical analysis employed the Statistica 7.0 computer program (Statsoft Inc.) with significance being set for a p-value < 0.05.

The XmnI polymorphism was observed in 36.5% of heterozygous beta-thalassemia patients and in 41.4% of control subjects. There was no statistically significant difference between the two groups (p-value = 0.32). There were significantly higher concentrations of Hb F (p-value = 0.01) in individuals with the polymorphism compared to those without (Table 1).

Table 1

Fetal hemoglobin concentrations in patients with heterozygous beta-thalassemia

		Xmn I Polymorphism
	+/+ (n=2)	+/- (n=55)	-/- (n=99)
Fetal hemoglobin concentration %	3.75 ±2.61	2.58 ±2.59*	1.55 ±1.98*

Data presented as means ± standard deviation

* Statistically significant difference between heterozygous and wild type homozygous individuals (Mann-Whitney test, p-value = 0.011)

The CD39 was found in 60.25% of cases, corroborating other published results that this is the most common mutation in Southeastern and Southern Brazil.(Additionally, the IVS-I-110 (25.64%) and IVS-I-6 (5.12%) were found as were other unidentified mutations (8.9%). There was no statistical difference between the presence of the XmnI polymorphism and beta thalassemia mutations (p = 0.99).

In conclusion, the XmnI polymorphism influences Hb F concentrations in patients with the beta-thalassemia trait. The presence of the polymorphic site showed no difference between heterozygous beta-thalassemia carriers and control subjects. The average levels of Hb F in individuals with heterozygous beta-thalassemia and with the XmnI polymorphism were higher than normal, showing the influence of this site on the gene expression of γ-globin.