Abstract：
Iron resistance iron deficiency anaemia is a rare autosomal recessive disorder characterized by hypochromic microcytic anaemia, low transferrin saturation and inappropriately high hepcidin levels. The aetiology of this condition is rooted in genetic variations within the transmembrane serine protease 6 (TMPRSS6) genes, responsible for encoding matriptase-2, a pivotal negative regulator of hepcidin. We conducted a systematic search across four electronic databases, yielding 538 articles in total out of which 25 were finally included and were preceded further, aiming to prognosticate prevalent single nucleotide polymorphisms (SNPs) and detrimental genetic alterations. This review aims to elucidate the effects of various SNPs and pathogenic mutations on both haematological and biochemical parameters, as well as their potential interethnic correlation. Employing bioinformatics tools, we subjected over 100 SNPs to scrutiny, discerning their potential functional ramifications. We found rs1373272804, rs1430692214 and rs855791 variants to be most frequent and were having a significant impact on haematological and biochemical profile. We found that individuals of European ancestry were more prone to have these variants compared to other ethnic groups. In conclusion, this review not only sheds light on the association of TMPRSS6 polymorphism in iron resistance iron deficiency anaemia (IRIDA), but also highlights the critical need for further investigations involving larger sample size and more diverse ethnic groups around the globe. These future studies will be vital for gaining a stronger and more reliable understanding of how these genetic differences are linked to the development of IRIDA.
摘要：
铁抗性缺铁性贫血是一种罕见的常染色体隐性遗传疾病，其特征是低色素性小细胞性贫血。低转铁蛋白饱和度和不适当的高铁调素水平。这种情况的病因植根于跨膜丝氨酸蛋白酶6（TMPRSS6）基因内的遗传变异，负责编码matriptase-2，铁调素的关键负调节因子。我们在四个电子数据库中进行了系统的搜索，总共产生538篇文章，其中25篇最终被纳入，并在进一步之前，旨在预测流行的单核苷酸多态性（SNP）和有害的遗传改变。这篇综述旨在阐明各种SNP和致病突变对血液和生化参数的影响。以及他们潜在的民族间关系。利用生物信息学工具，我们对100多个SNP进行了审查，辨别它们潜在的功能后果。我们发现rs1373272804，rs1430692214和rs855791变体最常见，并对血液学和生化特征产生重大影响。我们发现，与其他种族相比，欧洲血统的个体更容易出现这些变体。总之,本综述不仅阐明了TMPRSS6多态性与铁抗性缺铁性贫血(IRIDA)的关系,但也强调了对涉及全球更大样本量和更多样化种族群体的进一步调查的迫切需要。这些未来的研究对于获得更强大，更可靠的理解这些遗传差异如何与IRIDA的发展有关至关重要。
