Jallow Momodou W, Campino Susana, Saidykhan Alasana, Prentice Andrew M, Cerami Carla
MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, Banjul, The Gambia.
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Curr Dev Nutr. 2021 Feb 24;5(3):nzab014. doi: 10.1093/cdn/nzab014. eCollection 2021 Mar.
The role of genetic determinants in mediating iron status in Africans is not fully understood. Genome-wide association studies in non-African populations have revealed genetic variants in the transmembrane protease serine 6 gene () that are associated with the risk of anemia.
To investigate the effects of risk alleles for low iron status, namely rs2235321, rs855791, and rs4820268, on responses to oral iron in healthy Gambian adults.
Using a recall-by-genotype design, participants were selected from a pregenotype cohort of 3000 individuals in the Keneba Biobank (Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine). Participants were invited to participate in the study based on 9 genotype combinations obtained from 3 single nucleotide polymorphisms (SNPs): rs2235321, rs855791, and rs4820268. The participants fasted overnight and then ingested a single oral dose of ferrous sulfate (130 mg elemental iron). Blood samples were collected prior to iron ingestion and at 2 and 5 h after the oral iron dose. The effects of genotype on hepcidin and plasma iron parameters were assessed.
A total of 251 individuals were enrolled. Homozygous carriers of the major alleles at each of the SNPs had higher plasma hepcidin at baseline (rs2235321: GG compared with AA = 9.50 compared with 6.60 ng/ml, = 0.035; rs855791: GG compared with AG = 9.50 compared with 4.96 ng/mL, = 0.015; rs4820268: AA compared with GG = 9.50 compared with 3.27 ng/mL, = 0.002) and at subsequent timepoints. In most subjects, hepcidin concentrations increased following iron ingestion (overall group mean = 4.98 ± 0.98 ng/mL at 5 h, < 0.001), but double heterozygotes at rs2235321 and rs855791 showed no increase (0.36 ± 0.40 ng/mL at 5 h, = 0.667).
This study revealed that common variants influence hepcidin concentrations, but not iron status indicators either at baseline or following a large oral dose of iron. These results suggest that genetic variations in the gene are unlikely to be important contributors to variations in iron status in Africans.This study was registered at clinicaltrials.gov (# NCT03341338).
基因决定因素在调节非洲人铁状态中的作用尚未完全明确。在非非洲人群中进行的全基因组关联研究已揭示跨膜蛋白酶丝氨酸6基因（）中的基因变异与贫血风险相关。
探讨缺铁状态风险等位基因，即rs2235321、rs855791和rs4820268，对健康冈比亚成年人口服铁剂反应的影响。
采用基因分型回顾性设计，从凯内巴生物样本库（伦敦卫生与热带医学院冈比亚医学研究理事会单位）的3000名个体的基因分型前队列中选取参与者。根据从3个单核苷酸多态性（SNP）：rs2235321、rs855791和rs4820268获得的9种基因型组合邀请参与者参加研究。参与者空腹过夜，然后口服单剂量硫酸亚铁（130mg元素铁）。在摄入铁剂前以及口服铁剂后2小时和5小时采集血样。评估基因型对铁调素和血浆铁参数的影响。
共纳入251名个体。每个SNP的主要等位基因纯合携带者在基线时（rs2235321：GG与AA相比 = 9.50与6.60 ng/ml， = 0.035；rs855791：GG与AG相比 = 9.50与4.96 ng/mL， = 0.015；rs4820268：AA与GG相比 = 9.50与3.27 ng/mL， = 0.002）以及随后的时间点血浆铁调素水平较高。在大多数受试者中，摄入铁剂后铁调素浓度升高（总体组均值在5小时时为4.98 ± 0.98 ng/mL， < 0.001），但rs2235321和rs855791的双杂合子未升高（5小时时为0.36 ± 0.40 ng/mL， = 0.667）。
本研究表明常见变异影响铁调素浓度，但在基线时或口服大剂量铁剂后对铁状态指标无影响。这些结果表明该基因的遗传变异不太可能是非洲人铁状态变异的重要因素。本研究已在clinicaltrials.gov注册（#NCT03341338）。
