Modelling the mortality of sickle cell disease in Africa.
Modelling the mortality of sickle cell disease in Africa.
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对非洲镰状细胞病的死亡率进行建模。
DOI：
10.1016/s2352-3026(21)00268-4
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kengne,AndrePascal
中科院分区：
文献类型：
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作者：
Wonkam,Ambroise;Kengne,AndrePascal
Obiageli E Nnodu及其同事在《柳叶刀血液学》中介绍了他们的数据分析结果，估计了尼日利亚儿童镰状细胞病的死亡率，1尼日利亚是镰状细胞病负担最大的国家。他们正确地提到了2019年全球疾病负担研究或WorldPop中镰状细胞病死亡率的全球估计值可能被低估。因此，他们使用2018年尼日利亚人口和健康调查数据的模型估计分析，估计了尼日利亚6-59个月儿童的镰状细胞病死亡率。研究人员发现，预计尼日利亚镰状细胞病的儿童死亡率很高（2003年至2013年出生的镰状细胞病儿童的全国平均死亡率估计为每1000例活产490例[95% CI 270-700]）。重要的是，这项研究提供了一些方法上的创新，在特定条件下，这些创新可能对非洲其他环境有用，例如提供关于人口社会人口调查的全国最低限度信息，以及关于镰状细胞病的相关可靠筛查数据。虽然这项研究的模型很有吸引力，但它们严重依赖于哈迪-温伯格平衡的假设作为关键标准。Hardy-Weinberg平衡是一个原则，表明在没有引起变异的因素的情况下，群体中的遗传变异，如镰刀突变（HBB-βS; MIM 603903），将从一代到下一代保持不变。然而，对新生儿的筛查调查表明，非洲镰状细胞病严重偏离哈迪-温伯格平衡。2这种偏差受到疟疾地方性差异的影响，HbAS和HbAC基因携带者具有选择性生存优势（镰状细胞病的患病率可能会受到几个因素的影响，包括遗传修饰剂，环境因素如疟疾地方性和营养不良，以及社会经济因素如家庭收入）。完美的Hardy-Weinberg平衡假设HBB-βS具有完全隐性致死性（相对适合度= 0），而纯合子（HbSS）实际上具有0· 2的相对适合度（隐性致死性= 0· 8）。3哈迪-温伯格平衡的另一个先决条件是种群中的随机交配，但一些非洲国家的情况并非如此，这些国家的近亲繁殖率估计在20- 70%之间，特别是在北非4和尼日利亚。[5]假设Hardy-Weinberg平衡，预计高血缘比例会导致HbS和镰状细胞病的发生率比估计的要高得多。此外，镰状细胞病是纯单基因的假设只是部分正确的，并有助于进一步偏离哈代-温伯格平衡。影响死亡率的既定遗传因素，如胎儿血红蛋白F（HbF）浓度，HbF调节基因座的相关变异，如BCL 11 A（MIM 606557），以及α地中海贫血（MIM 604131）变异的共同遗传，也应考虑在内。在肯尼亚的一项前瞻性队列研究6和美国的一项合作研究中，HbF浓度和α-地中海贫血都被证明是儿童死亡率的调节因素。7在喀麦隆的一项研究中，8 3· 7 kb α-珠蛋白基因缺失的共遗传与儿童镰状细胞病临床表现的延迟发作有关，并且在镰状细胞病患者中更常见。（约40%对对照组20%），在非洲的几个环境中发现了这一趋势，9表明α-地中海贫血有助于改善患者的生存...
In The Lancet Haematology, Obiageli E Nnodu and colleagues presented the findings of their data analysis estimating the mortality of sickle cell disease in children in Nigeria, 1 the country with the largest sickle cell disease burden. They rightfully mentioned the possible underestimation of available global estimates of sickle cell disease mortality from the 2019 Global Burden of Disease study or WorldPop. Therefore they estimated mortality from sickle cell disease in children aged 6–59 months in Nigeria using a model-estimated analysis of data from the 2018 Nigerian Demographic and Health Survey. The investigators found an expected high child mortality rate of sickle cell disease in Nigeria (estimated national average under-5 mortality for children with sickle cell disease born between 2003 and 2013 was 490 per 1000 live births [95% CI 270–700]). Importantly, the study provides some methodological innovations which could be useful in other African settings, under specific conditions, such as the availability of nationwide minimal information on populations socio-demographic survey, with associated reliable screening data on sickle cell disease. Although the study’s models are attractive, they relied heavily on the assumption of Hardy-Weinberg equilibrium as a critical criterion. Hardy-Weinberg equilibrium is a principle stating that genetic variation in a population, such as sickle mutation (HBB-βS; MIM 603903), will remain constant from one generation to the next in the absence of factors that cause variation. However, screening surveys of newborn babies have shown that there is a major deviation from Hardy-Weinberg equilibrium in sickle cell disease in Africa. 2 This deviation is influenced by differential malaria endemicity, with individuals who are carriers of the HbAS and HbAC genes having a selective survival advantage (prevalence of sickle cell disease might be altered by several factors including genetic modifiers, environmental factors such as malaria endemicity and malnutrition, and socioeconomic factors such as household income). A perfect Hardy-Weinberg equilibrium assumes a complete recessive lethality of HBB-βS (relative fitness= 0), whereas homozygotes (HbSS) actually have a relative fitness of 0· 2 (recessive lethality= 0· 8). 3 Another pre-requisite of the Hardy-Weinberg equilibrium is random mating in the population, which is not the case in some African countries, where the consanguinity rate is estimated between 20–70%, particularly in North Africa4 and Nigeria. 5 High rates of consanguinity should be expected to lead to a much higher frequency of HbS and sickle cell disease than estimated, assuming Hardy-Weinberg equilibrium. Moreover, the assumption that sickle cell disease is purely monogenic is only partly correct and contributes to further departure from Hardy-Weinberg equilibrium. Established genetic factors that influence mortality, such as fetal haemoglobin F (HbF) concentrations, related variants in HbF-modulating loci such as in BCL11A (MIM 606557), and coinheritance of alphathalassaemia (MIM 604131) variants, should also be accounted for. Both HbF concentration and alpha-thalassaemia were shown to be modifiers of childhood mortality in a prospective cohort in Kenya, 6 and a cooperative study in the USA. 7 In a study in Cameroon, 8 the coinheritance of 3· 7 kb α-globin gene deletion was associated with delayed onset of clinical manifestations of sickle cell disease in children and occurred more frequently in individuals with sickle cell disease (around 40% vs 20% in controls), a trend found in several settings in Africa, 8, 9 suggesting that alpha-thalassaemia contributes to improved survival of patients …
DOI：
10.1038/gim.2015.143
发表时间：
2016-03
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Piel FB;Adamkiewicz TV;Amendah D;Williams TN;Gupta S;Grosse SD
通讯作者：
Grosse SD
影响因子：
3.7
作者：
Rumaney MB;Ngo Bitoungui VJ;Vorster AA;Ramesar R;Kengne AP;Ngogang J;Wonkam A
通讯作者：
Wonkam A