Table 2.
Associations between rs855791 in the transmembrane serine protease 6 gene (TMPRSS6) and rs1800562 in the haemochromatosis gene (HFE) with iron parameters for the total study population (N=1832)
| Additionally adjusted for: | Total N* | p Value | AG | AA | |||
|---|---|---|---|---|---|---|---|
| N | β AG vs GG (95% CI) | N | β AA vs GG (95% CI) | ||||
| TMPRSS6 rs855791† | |||||||
| Log(hepcidin)‡, nM | NA | 1824 | 2.02E-01 | 928 | 0.01 (−0.03 to 0.05) | 365 | 0.05 (−0.01 to 0.10) |
| Log(ferritin), μg/L‡ | NA | 1822 | 1.86E-01 | 926 | −0.03 (−0.07 to 0.01) | 365 | −0.04 (−0.09 to 0.01) |
| Log(hepcidin) | 1822 | 1.36E-05 | 926 | −0.04 (−0.06 to −0.01) | 365 | −0.07 (−0.10 to −0.04) | |
| Log(hepcidin/ferritin)‡, nmoles/μg | NA | 1822 | 8.60E-06 | 926 | 0.04 (0.01 to 0.07) | 365 | 0.08 (0.05 to 0.12) |
| Log(hepcidin/TS)‡, nM/% | NA | 1804 | 3.42E-05 | 919 | 0.05 (0.01 to 0.09) | 358 | 0.12 (0.07 to 0.17) |
| Iron, μM | NA | 1804 | 3.36E-12 | 919 | −1.50 (−2.06 to −0.93) | 358 | −2.53 (−3.24 to −1.82) |
| Log(hepcidin) | 1804 | 6.71E-13 | 919 | −1.51 (−2.08 to −0.95) | 358 | −2.60 (−3.31 to −1.90) | |
| Log(hepcidin/ferritin) | 1804 | 7.90E-11 | 919 | −1.42 (−1.98 to −0.86) | 358 | −2.37 (−3.08 to −1.66) | |
| TS, % | NA | 1804 | 8.47E-14 | 919 | −2.92 (−3.96 to −1.89) | 358 | −4.96 (−6.26 to −3.66) |
| Log(hepcidin) | 1804 | 1.48E-15 | 919 | −2.98 (−3.99 to −1.96) | 358 | −5.21 (−6.48 to −3.94) | |
| Log(hepcidin/ferritin) | 1804 | 1.54E-12 | 919 | −2.81 (−3.84 to −1.77) | 358 | −4.71 (−6.01 to −3.41) | |
| TIBC, μM | NA | 1804 | 1.27E-01 | 919 | 0.74 (−0.20 to 1.68) | 358 | 1.16 (−0.02 to 2.33) |
| Log(hepcidin) | 1804 | 2.57E-02 | 919 | 0.82 (−0.07 to 1.71) | 358 | 1.51 (0.40 to 2.63) | |
| Log(hepcidin/ferritin) | 1804 | 7.87E-02 | 919 | 0.81 (−0.13 to 1.75) | 358 | 1.30 (0.11 to 2.48) | |
| HFE rs1800562† | |||||||
| Log(hepcidin)‡, nM | NA | 1824 | 3.89E-01 | 217 | 0.00 (−0.06 to 0.05) | 4 | −0.27 (−0.66 to 0.12) |
| Log(ferritin), μg/L‡ | NA | 1822 | 2.01E-04 | 216 | 0.04 (−0.01 to 0.10) | 4 | 0.69 (0.33 to 1.04) |
| Log(hepcidin) | 1822 | 2.08E-15 | 216 | 0.05 (0.01 to 0.08) | 4 | 0.88 (0.66 to 1.11) | |
| Log(hepcidin/ferritin)‡, nmoles/μg | NA | 1822 | 1.35E-07 | 216 | −0.04 (−0.08 to −0.01) | 4 | −0.65 (−0.90 to −0.41) |
| Log(hepcidin/TS)‡, nM/% | NA | 1804 | 5.73E-04 | 212 | −0.07 (−0.13 to −0.02) | 4 | −0.58 (−0.96 to −0.20) |
| Iron, μM | NA | 1804 | 1.39E-11 | 212 | 2.26 (1.50 to 3.02) | 4 | 10.71 (5.53 to 15.88) |
| Log(hepcidin) | 1804 | 5.70E-12 | 212 | 2.26 (1.51 to 3.02) | 4 | 11.09 (5.94 to 16.24) | |
| Log(hepcidin/ferritin) | 1804 | 3.33E-10 | 212 | 2.18 (1.42 to 2.93) | 4 | 9.33 (4.15 to 14.52) | |
| TS, % | NA | 1804 | 7.00E-18 | 212 | 5.36 (3.98 to 6.75) | 4 | 22.60 (13.17 to 32.04) |
| Log(hepcidin) | 1804 | 3.20E-19 | 212 | 5.37 (4.02 to 6.73) | 4 | 23.93 (14.68 to 33.18) | |
| Log(hepcidin/ferritin) | 1804 | 1.85E-16 | 212 | 5.24 (3.87 to 6.62) | 4 | 20.58 (11.10 to 30.06) | |
| TIBC, μM | NA | 1804 | 1.17E-06 | 212 | −3.05 (−4.30 to −1.80) | 4 | −9.58 (−18.13 to −1.02) |
| Log(hepcidin) | 1804 | 6.81E-08 | 212 | −3.06 (−4.25 to −1.88) | 4 | −11.51 (−19.61 to −3.41) | |
| Log(hepcidin/ferritin) | 1804 | 3.44E-07 | 212 | −3.13 (−4.38 to −1.88) | 4 | −10.94 (−19.54 to −2.33) | |
Associations are adjusted for age, gender, time of blood sampling, and additionally for serum hepcidin or the ratio hepcidin/ferritin.
N indicates number; β AG vs GG, regression coefficient for AG genotype versus GG genotype; β AA versus GG, regression coefficient for AA genotype versus GG genotype.
For TMPRSS6 rs855791 (p.Ala736Val), minor allele is A with frequency 0.455 in the whole cohort. Therefore, genotype GG is used as the reference genotype.
For HFE rs1800562 (p.Cys282Tyr), minor allele is A with frequency 0.063 in the whole cohort. Therefore, genotype GG is used as the reference genotype.
Numbers are different from the total number of included persons because of missing values.
Both SNPs are genotyped.
The dependent variables hepcidin, ferritin, hepcidin/ferritin, and hepcidin/TS were log-transformed. Therefore, the regression coefficients express the changes in each log-transformed variable that are associated with each genotype relative to the reference genotype.
SNP, single nucleotide polymorphisms; TIBC, total iron binding capacity; TS, transferrin saturation.