Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.
Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.
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DOI：
10.1371/journal.pone.0157996
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Melse-Boonstra A
中科院分区：
文献类型：
--
作者：
Gichohi-Wainaina WN;Tanaka T;Towers GW;Verhoef H;Veenemans J;Talsma EF;Harryvan J;Boekschoten MV;Feskens EJ;Melse-Boonstra A
对欧洲血统个体的大型全基因组关联（GWA）研究已经确定了影响铁状态的多种遗传变异。关于这些关联对非洲血统人群的普遍性的研究有限。这些研究是重要的，因为不同种族之间的铁状况和非洲血统人群中不成比例的铁缺乏负担的差异。我们在628名肯尼亚人、609名坦桑尼亚人、608名南非人和228名非洲裔美国人中检测了20种先前确定的铁状态相关单核苷酸多态性（SNP）的相关性。在每项研究中，我们检查了20个SNP与铁蛋白和血红蛋白之间的关联，调整了年龄，性别和CRP水平。在包括所有4个非洲血统队列的Meta分析中，我们重复了TMPRSS中rs 2413450（β =-0.19，P = 0.02）和rs 4820268（β =-0.16，P = 0.04）与血红蛋白浓度降低的相关性6。在仅包括非洲队列的Meta分析中，也证实了TF中rs 1867504与铁蛋白浓度增加的相关性（β = 1.04，P = <0.0001）。在所有的Meta分析中，我们只复制了20个单核苷酸多态性中的4个，这些单核苷酸多态性与欧洲血统个体的大型GWA研究中的铁状态相关。虽然现在有证据表明，在欧洲和非洲血统的人群中，一些遗传变异与铁的状态有关，但相当程度的不一致性突出了继续进行祖先特异性研究的重要性，以阐明不同种族人群铁状态的遗传基础。
Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.