TF、TNF-α和TMPRSS6基因中的常见变异和单倍型与南非黑人女性人群的铁状态相关。

Common Variants and Haplotypes in the TF, TNF-α, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population.

作者信息

Gichohi-Wainaina Wanjiku N, Melse-Boonstra Alida, Swinkels Dorine W, Zimmermann Michael B, Feskens Edith J, Towers G Wayne

机构信息

Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;

The Laboratory of Genetic, Endocrine, and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;

出版信息

J Nutr. 2015 May;145(5):945-53. doi: 10.3945/jn.114.209148. Epub 2015 Mar 25.

DOI:10.3945/jn.114.209148

PMID:25809685

Abstract

BACKGROUND

It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population.

OBJECTIVES

We investigated associations of reported SNPs with iron markers in a South African cohort.

METHODS

Hemoglobin concentration, serum ferritin (SF) and soluble transferrin receptor (sTfR) concentrations, and body iron (BI) stores were measured in women (n = 686; range, 32-86 y) who were part of the Prospective Urban and Rural Epidemiology study. Thirty-two SNPs in 12 genes were selected based on existing genome-wide association study data.

RESULTS

In the transferrin (TF) gene, SF and BI were significantly lower in the heterozygote genotype (AG) of reference SNP (rs) 1799852 (P = 0.01 and 0.03, respectively) and sTfR concentrations were significantly higher (P = 0.004) than the homozygote minor allele genotype (AA), whereas transferrin receptor and BI concentrations were significantly lower in the heterozygote genotype (AG) of rs3811647 (both P = 0.03) than the homozygote wild-type (AA) and minor allele groups (GG). The chromosome 6 allele combination (AAA) consisting of rs1799964 and rs1800629 both in tumor necrosis factor-α (TNF-α) and rs2071592 in nuclear factor κB inhibitor-like protein 1 (NFKBIL1) was associated with higher odds for low SF concentrations (SF < 15 μg/L; OR: 1.86; 95% CI: 1.23, 2.79) than the allele combinations AGA, GGT, and AGT. The chromosome 22 allele combination (GG) consisting of rs228918 and rs228921 in the transmembrane protease serine 6 (TMPRSS6) gene was associated with lower odds for increased sTfR concentrations (sTfR > 8.3mg/L; OR: 0.79; 95% CI: 0.63, 0.98) than the allele combination AA.

CONCLUSIONS

Various SNPs and allele combinations in the TF, TNF-α, and TMPRSS6 genes are associated with iron status in black South African women; however, these association patterns are different compared with European ancestry populations. This stresses the need for population-specific genomic data.

摘要

背景

在欧洲和亚洲人群中与铁状态相关的单核苷酸多态性（SNP）在非洲人群中是否具有相同的关系尚不清楚。

目的

我们在一个南非队列中研究了已报道的SNP与铁标志物之间的关联。

方法

在参与城乡前瞻性流行病学研究的女性（n = 686；年龄范围32 - 86岁）中测量血红蛋白浓度、血清铁蛋白（SF）、可溶性转铁蛋白受体（sTfR）浓度和机体铁（BI）储存量。基于现有的全基因组关联研究数据，在12个基因中选择了32个SNP。

结果

在转铁蛋白（TF）基因中，参考单核苷酸多态性（rs）1799852的杂合子基因型（AG）中的SF和BI显著低于纯合子次要等位基因基因型（AA）（分别为P = 0.01和0.03），而sTfR浓度显著高于纯合子次要等位基因基因型（AA）（P = 0.004）；而rs3811647的杂合子基因型（AG）中的转铁蛋白受体和BI浓度显著低于纯合子野生型（AA）和次要等位基因组（GG）（均为P = 0.03）。由肿瘤坏死因子-α（TNF-α）中的rs1799964和rs1800629以及核因子κB抑制蛋白样蛋白1（NFKBIL1）中的rs2071592组成的6号染色体等位基因组合（AAA）与低SF浓度（SF < 15 μg/L）的较高比值相关（比值比：1.86；95%置信区间：1.23，2.79），高于等位基因组合AGA、GGT和AGT。由跨膜蛋白酶丝氨酸6（TMPRSS6）基因中的rs228918和rs228921组成的22号染色体等位基因组合（GG）与sTfR浓度升高（sTfR > 8.3mg/L）的较低比值相关（比值比：0.79；95%置信区间：0.63，0.98），低于等位基因组合AA。