Ferrara Mara, Matarese Sofia M R, Francese Matteo, Borrelli Barbara, Perrotta Angelo, Meo Anna, La Rosa Maria A, Esposito Luigi
Department of Pediatrics, Second University of Naples, Naples, Italy.
Hemoglobin. 2003 Aug;27(3):167-75. doi: 10.1081/hem-120023380.
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.
67名年龄在8至33岁之间、具有不同表型的纯合子男性和女性地中海贫血患者，根据其β-地中海贫血（地贫）突变的严重程度分为三组。我们研究了一些共同遗传的基因因素是否会影响表型。β-地贫缺陷较轻的患者，即IVS-I-6（T→C）或-87（C→G）突变的纯合子或复合杂合子，病情较轻。此外，对β-珠蛋白基因5'端-540至-525区域内-158（C→T）G（γ）多态性和（AT）9T5重复基序的共同遗传情况进行测定，结果显示，在一些与单倍型III相关的重度或轻度/重度β-地贫突变患者中，Hb F表达较高。我们得出结论，在纯合子β-地贫患者中，突变的严重程度是影响表型的最重要因素，但一些多态性，如-158（C→T）G（γ）和（AT）9T5重复基序，可增加Hb F表达并改善疾病的临床进程。
