Association of TMPRSS6 gene polymorphisms with severity of iron deficiency anemia in Uzbek schoolchildren: a molecular case-control study

Iron deficiency anemia (IDA) is one of the most common nutritional disorders worldwide and is particularly prevalent among children, where/in whom it may impair cognitive development, physical performance, and immune function [1,2].Although nutritional deficiency remains the primary cause, genetic factors also contribute to variability in iron metabolism and disease severity.The TMPRSS6 gene plays a key role in regulating hepcidin expression, and its polymorphisms have been associated with altered iron status [3].Previous studies have demonstrated interethnic differences in TMPRSS6 variants and their association with iron-related biomarkers [4].However, data on TMPRSS6 gene polymorphisms in Central Asian pediatric populations remain limited.In particular, there is insufficient information regarding the distribution of these variants and their association with the severity of IDA among Uzbek schoolchildren.This study provides novel evidence on the relationship between TMPRSS6 polymorphisms (rs855791, rs4820268, and rs11704654) and the clinical severity of iron deficiency anemia.By analyzing allele and genotype distributions across different severity groups, the study highlights a potential role of these variants in disease progression.These findings help address an important regional data gap and may support the development of population-specific approaches for early risk assessment and prevention of IDA.Methods.Study design and participants.This case-control study was conducted in the Fergana Valley region (Fergana, Andijan, and Namangan).A total of 784 schoolchildren were initially screened for iron deficiency, from which 101 children diagnosed with IDA were selectively enrolled for molecular-genetic analysis.Additionally, 100 age-matched healthy children with no clinical or laboratory evidence of anemia were included as a control group.The final cohort of 201 participants was stratified by IDA severity using standard WHO-aligned criteria: mild (Hb 90-110 g/l), moderate (Hb 70-89 g/l), and severe (Hb < 70 g/l).Clinical and laboratory assessment.Peripheral blood samples were collected under standardized conditions.Hemoglobin concentration and erythrocyte indices were measured using routine laboratory methods.DNA extraction and genotyping.Genomic DNA was extracted from peripheral blood leukocytes using standard procedures.