Milman Nils Thorm
Department of Clinical Biochemistry, Naestved Hospital, University of Zealand, DK-4700 Naestved, Denmark. Email:
Gastroenterology Res. 2025 Apr;18(2):63-70. doi: 10.14740/gr2021. Epub 2025 Mar 18.
The ethnic Danish population has high frequencies of the hemochromatosis gene ( gene) variants H63D and C282Y and clinical hemochromatosis is quite common. The objective of the study was to examine the impact of the combination of the variants wildtype (wt), H63D, and C282Y on body iron status markers in a population of 2,613 apparently healthy ethnic Danish men and women.
An epidemiological population study was performed in Copenhagen County comprising a randomly selected population consisting of 1,342 men and 1,271 women. Blood samples were drawn in the morning in the fasting state for analysis of genotypes and hematological iron status markers (hemoglobin, serum iron, serum transferrin, transferrin saturation, and serum ferritin).
The gene variants, H63D and C282Y, in any combination as well as in any combination with the wt genotype, had a significant influence on iron status markers, compared with the wt/wt genotype. When arranged according to their relative frequency in the population, individuals with the six different genotypes, i.e. wt/wt, H63D/wt, C282Y/wt, H63D/H63D, C282Y/H63D, and C282Y/C282Y, displayed gradually increasing levels of serum iron, decreasing levels of serum transferrin, and increasing levels of transferrin saturation in both genders. In men, ferritin increased gradually according to the genotype. In women, ferritin levels were by and large independent of the genotypes.
Using the iron status markers in wt/wt individuals as a baseline, any other combination of the genotypes had a significant impact on iron status. The C282Y/C282Y genotype was associated with the highest impact on iron status markers including serum ferritin and thus body iron overload. Due to physiological iron losses with menstruations and pregnancies, women are partly protected against significant body iron overload, regardless of the genotype.
丹麦族人群中血色素沉着症基因（基因）变体H63D和C282Y的频率较高，临床血色素沉着症相当常见。本研究的目的是在2613名看似健康的丹麦族男性和女性人群中，研究野生型（wt）、H63D和C282Y这几种变体组合对机体铁状态标志物的影响。
在哥本哈根郡进行了一项流行病学人群研究，随机选取了1342名男性和1271名女性组成研究人群。在早晨空腹状态下采集血样，用于分析基因分型和血液学铁状态标志物（血红蛋白、血清铁、血清转铁蛋白、转铁蛋白饱和度和血清铁蛋白）。
与wt/wt基因型相比，H63D和C282Y这两种基因变体的任何组合，以及与wt基因型的任何组合，对铁状态标志物均有显著影响。按照它们在人群中的相对频率排列，具有六种不同基因分型，即wt/wt、H63D/wt、C282Y/wt、H63D/H63D、C282Y/H63D和C282Y/C282Y的个体，无论男女，血清铁水平逐渐升高，血清转铁蛋白水平逐渐降低，转铁蛋白饱和度逐渐升高。在男性中，铁蛋白水平根据基因分型逐渐升高。在女性中，铁蛋白水平大体上与基因分型无关。
以wt/wt个体的铁状态标志物为基线，基因分型的任何其他组合对铁状态均有显著影响。C282Y/C282Y基因型对包括血清铁蛋白在内的铁状态标志物影响最大，从而导致机体铁过载。由于月经和怀孕会导致生理性铁流失，女性在一定程度上受到保护，不会出现显著的机体铁过载，无论其基因分型如何。
