镰状血红蛋白与胎儿血红蛋白之间的负上位性表明对疟疾的保护作用降低。
Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in Protection against Malaria.
作者信息
Mmbando Bruno P, Mgaya Josephine, Cox Sharon E, Mtatiro Siana N, Soka Deogratias, Rwezaula Stella, Meda Elineema, Msaki Evarist, Snow Robert W, Jeffries Neal, Geller Nancy L, Makani Julie
机构信息
Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania; National Institute for Medical Research, Tanga, Tanzania.
Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.
出版信息
PLoS One. 2015 May 12;10(5):e0125929. doi: 10.1371/journal.pone.0125929. eCollection 2015.
BACKGROUND
Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection.
METHODS
The study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tanzania. SCD status was categorized into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was diagnosed using rapid diagnostic test and/or blood film. Logistic regression and generalized estimating equations models were used to evaluate associations between SCD status, HbF and malaria.
FINDINGS
2,049 individuals with age range 0-70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed. At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared to HbAS 1.24% and HbSS 1.34% (p<0.001). Mean HbF was lower in those with malaria compared to those without malaria in HbAA (0.43% vs 0.82%) but was the reverse in HbSS (8.10% vs 5.59%). An increase in HbF was associated with a decrease in risk of malaria OR=0.50 (95%CI: 0.28, 0.90; p=0.021) in HbAA, whereas for HbSS the risk of malaria increased OR=2.94 (1.44, 5.98; p=0.003). A similar pattern was seen during multiple visits; HbAA OR=0.52 (0.34, 0.80; p=0.003) vs HbSS OR=2.01 (1.27, 3.23; p=0.003).
CONCLUSION
Higher prevalence of malaria in HbAA compared to HbAS and HbSS confirmed the protective effect of HbS. Lower prevalence of malaria in HbAA with high HbF supports a protective effect of HbF. However, in HbSS, the higher prevalence of malaria with high levels of HbF suggests loss of malaria protection. This is the first epidemiological study to suggest a negative epistasis between HbF and HbS on malaria.
背景
血红蛋白变异体，如镰状血红蛋白（HbS）和胎儿血红蛋白（HbF）与疟疾保护有关。本研究探讨了HbS和HbF在疟疾感染上的上位性相互作用。
方法
该研究于2004年3月至2013年12月在坦桑尼亚姆希比利国家医院的镰状细胞病（SCD）项目中进行。使用血红蛋白电泳和高效液相色谱法（HPLC）将SCD状态分为HbAA、HbAS和HbSS。通过HPLC测定HbF水平。使用快速诊断试验和/或血涂片诊断疟疾。采用逻辑回归和广义估计方程模型评估SCD状态、HbF与疟疾之间的关联。
结果
分析了2049名年龄在0至70岁之间的个体，其中HbAA 311例（15.2%），HbAS 241例（11.8%），HbSS 1497例（73.1%）。在入组时，HbAA的疟疾患病率显著高于HbAS（1.24%）和HbSS（1.34%），为13.2%（p<0.001）。在HbAA中，患疟疾者的平均HbF低于未患疟疾者（0.43%对0.82%），但在HbSS中情况相反（8.10%对5.59%）。HbF升高与HbAA中疟疾风险降低相关，比值比（OR）=0.50（95%置信区间：0.28，0.90；p=0.021），而对于HbSS，疟疾风险增加，OR=2.94（1.44，5.98；p=0.003）。在多次随访中也观察到类似模式；HbAA的OR=0.52（0.34，0.80；p=0.003），而HbSS的OR=2.01（1.27，3.23；p=0.003）。
结论
与HbAS和HbSS相比，HbAA中疟疾患病率更高，证实了HbS的保护作用。HbF水平高的HbAA中疟疾患病率较低，支持了HbF的保护作用。然而，在HbSS中，HbF水平高时疟疾患病率更高，表明疟疾保护作用丧失。这是第一项表明HbF和HbS在疟疾上存在负上位性的流行病学研究。
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