Bittencourt P L, Palácios S A, Couto C A, Cançado E L R, Carrilho F J, Laudanna A A, Kalil J, Gayotto L C C, Goldberg A C
Hospital Português de Salvador, Salvador, BA, Brasil.
Braz J Med Biol Res. 2002 Mar;35(3):329-35. doi: 10.1590/s0100-879x2002000300007.
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.
血色素沉着症基因HFE位于6号染色体上,与HLA - A基因座紧密相邻。大多数患有遗传性血色素沉着症(HH)的白种人患者为HLA - A3纯合子,且HFE基因存在C282Y突变,而少数患者为C282Y和H63D的复合杂合子。这些突变在非白种人HH患者中的患病率低于预期。本研究的目的是评估巴西HH患者中HLA - A抗原的频率以及HFE基因的C282Y和H63D突变情况,并比较HH患者中C282Y阳性和阴性患者的临床和实验室特征。通过基于聚合酶链反应(PCR)的方法,对15名患有HH的男性患者(中位年龄44(20 - 72)岁)进行了HLA - A以及C282Y和H63D突变频率的测定。8名患者(53%)为C282Y突变纯合子,1名患者(7%)为C282Y突变杂合子。无人为C282Y和H63D突变的复合杂合子。除3名C282Y纯合子外,其余均为HLA - A3阳性,另外3名无C282Y突变的患者被检测为HLA - A3杂合子(N = 2)或纯合子(N = 1)。C282Y突变纯合子患者的铁蛋白水平较高,发病年龄较低,但差异不显著。大约一半的巴西HH患者存在C282Y纯合子,同时C282Y阴性受试者中存在HLA - A纯合子的情况,这表明HFE基因或其他参与铁稳态的基因中的其他突变在巴西可能也与HH有关。