|Beitragstitel||Association of zinc excretion with a SLC30A2 variant in the SKIPOGH study|
Background: Zinc is an essential element in human physiology. About 3,000 proteins display specific zinc binding motifs and fulfill a wide array of functions. More than 20 zinc transporters have been described and characterized, yet some uncertainty persists regarding zinc homeostasis in the human body. Imbalances in zinc homoeostasis can lead to impairments in immune function, growth, cognitive performance as well as glucose homeostasis.
Methods: Zinc excretion was measured in 24 hr urine using ICP-MS, with separate day and night collections, in 938 participants of the SKIPOGH cohort. Genome-wide SNP data were generated using the Illumina Omni 2.5 chip and imputed to the HRC v1.1 panel. DNA methylation at 450K loci was measured in white-blood cells of 235 participants with the Illumina HumanMethylation450 BeadChip.
Results: Genome-wide association of 24-hour urinary zinc excretion identified a locus on chromosome 1 near the SLC30A2 zinc transporter gene (rs3121763, P<1.0e^-12). The G allele of rs3121763 was associated with higher 24-hour urinary zinc excretion. Carriers of the ancestral allele (MAF 23.8% in SKIPOGH) have a higher excretion of zinc compared to non-carriers (z > 5 ).Differential DNA-methylation analysis revealed one CpG located in SLC30A2 to be hyper-methylated in carriers. Finally, the distribution of rs3121763 G allele substantially differs across populations of the 1000 Genomes Project, with higher frequency of the G allele in populations of African descent compared to other populations.
Discussion and outlook: We have unveiled a previously unknown association of variants located in the zinc transporter SLC30A2 to zinc homeostasis in the adult population. Preliminary results suggest an epigenetic modification at this locus, which may point towards differential expression of the SLC30A2 gene depending on dietary zinc intake. This finding may have a clinical and public health impact as even subclinical zinc deficiency can impair biological function. The higher prevalence of the G allele, associated with higher urinary zinc excretion in populations of African descent, suggests an evolutionary advantage in settings with low nutritional zinc bioavailability.