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Background & Aims Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. Methods We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. Results One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7 × 10-9 and replication p value of 5 × 10-13). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9 × 10-6 and replication p value of 3.2 × 10-6). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p <0.01). Serum iron levels were also associated with fibrosis stage (p <0.0001). Conclusions This GWAS, the largest one performed so far in unselected HFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely.

We demonstrate a method to reduce the mode volume of optical micro/nanocavities by positioning an opaque microtip in close proximity of the structures. This concept is used to blueshift the resonance of an active photonic crystal nanocavity by up to 16 nm. This tuning range is shown to be about 10 times larger than the redshift achieved with a bare dielectric microtip of the same size and shape. By imagining materials or multilayered devices with the ability to become transparent and opaque under external control, the blue and redshifts of the resonance would become possible with a single perturbing device. © 2012 American Institute of Physics.

We demonstrate a method to reduce the mode volume of optical micro/nanocavities by positioning an opaque microtip in close proximity of the structures. This concept is used to blueshift the resonance of an active photonic crystal nanocavity by up to 16 nm. This tuning range is shown to be about 10 times larger than the redshift achieved with a bare dielectric microtip of the same size and shape. By imagining materials or multilayered devices with the ability to become transparent and opaque under external control, the blue and redshifts of the resonance would become possible with a single perturbing device. © 2012 American Institute of Physics.