Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health sciences, Ghent University, Belgium.
Ann Hematol. 2012 Jun;91(6):911-6. doi: 10.1007/s00277-011-1400-3. Epub 2012 Jan 17.
The Q248H mutation in the gene SLC40A1 which encodes for the cellular iron exporter ferroportin is relatively common in Africa. This mutation has been associated with resistance to hepcidin and therefore we hypothesized that iron-related parameters and the prevalence of opportunistic infections in HIV might be influenced by the Q248H mutation. We conducted a cross-sectional study among 200 HIV-positive women in the Butare University Teaching Hospital in Rwanda. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Physical examination was carried out and WHO HIV disease stage classification, complete blood count, CD4 count, indirect measures of iron status, serum hepcidin, and C-reactive protein concentrations were determined. The prevalence of ferroportin Q248H mutation was 6%. Subjects with ferroportin Q248H mutation had significantly higher values for serum ferritin (P = 0.001) and significantly lower values for serum hepcidin (P = 0.001) and transferrin (P = 0.01). Among the 12 HIV + Q248H heterozygotes, 8 suffered from at least one opportunistic infection. There was significantly higher prevalence of pulmonary TB (P = 0.01) and Pneumocystis jiroveci pneumonia (P = 0.02) in subjects with ferroportin Q248H mutation. Low hepcidin levels were found in ferroportin Q248H heterozygotes with HIV infection, notwithstanding the absence of anemia and the higher prevalence of some opportunistic infections. Hepcidin seems to be regulated in a different way in Q248H heterozygotes than is known thus far.
SLC40A1 基因中的 Q248H 突变相对常见于非洲，该基因编码细胞铁输出蛋白——亚铁转运蛋白。该突变与对铁调素的抵抗有关，因此我们假设 HIV 患者的铁相关参数和机会性感染的发生率可能受到 Q248H 突变的影响。我们在卢旺达布塔雷大学教学医院进行了一项横断面研究，纳入了 200 名 HIV 阳性女性。聚合酶链反应（PCR）和限制性内切酶消化用于鉴定 Q248H 突变。进行了体格检查，并确定了世界卫生组织 HIV 疾病分期分类、全血细胞计数、CD4 计数、铁状态的间接指标、血清铁调素和 C 反应蛋白浓度。亚铁转运蛋白 Q248H 突变的患病率为 6%。携带亚铁转运蛋白 Q248H 突变的受试者血清铁蛋白值显著升高（P=0.001），血清铁调素（P=0.001）和转铁蛋白（P=0.01）值显著降低。在 12 名 HIV+Q248H 杂合子中，有 8 名至少患有一种机会性感染。携带亚铁转运蛋白 Q248H 突变的受试者中，肺结核（P=0.01）和卡氏肺孢子虫肺炎（P=0.02）的患病率明显更高。尽管存在贫血和某些机会性感染的患病率较高，但在携带亚铁转运蛋白 Q248H 突变的 HIV 感染者中发现铁调素水平较低。铁调素在 Q248H 杂合子中的调节方式似乎与目前已知的方式不同。
