SLC30A8 promoter hypermethylation is associated with type 2 diabetes and diabetic kidney disease in a Chinese population

Figure 1 Association of solute carrier family 30 member 8 promoter hypermethylation with both type 2 diabetes and diabetic kidney disease. A: Solute carrier family 30 member 8 promoter methylation levels in the groups of non-diabetic control, newly diagnosed type 2 diabetes, type 2 diabetes and diabetic kidney disease; B: DNA methylation levels at six CpG sites of solute carrier family 30 member 8 promoter region. T2D: Type 2 diabetes; DKD: Diabetic kidney disease.

Figure 2 Mendelian randomization analysis reveals a causal relationship between decreased solute carrier family 30 member 8 expression and higher risk of type 2 diabetes. A: The quantitative trait loci data from East Asian populations and genome wide association study for type 2 diabetes as the outcome are used for Mendelian randomization analysis; B: The multiple Mendelian randomization methods are implemented using solute carrier family 30 member 8 expression as the exposure and type 2 diabetes as the outcome; C-E: Each instrumental variable’s contribution is assessed to the inverse variance weighted method. GWAS: Genome wide association study; SNP: Single nucleotide polymorphisms; QTL: Quantitative trait loci; SLC30A8: Solute carrier family 30 member 8; MR: Mendelian randomization; LD: Linkage disequilibrium; OR: Odds ratio; CI: Confidence interval.

Figure 3 DNA methylation changes of solute carrier family 30 member 8 in kidneys of db/db mice and pancreatic tissues of serous cystadenoma patients. A: Solute carrier family 30 member 8 (SLC30A8) is expressed in the proximal convoluted tubule and collecting duct principal cells of kidneys, which is predicted by single cell-RNA sequencing analysis. B and C: SLC30A8 DNA methylation and RNA expression levels in whole kidney of db/db mice with diabetic kidney disease and without diabetic kidney disease; D: SLC30A8 promoter hypermethylation exists in pancreatic tissue of pancreatic serous cystadenoma patients with and without type 2 diabetes; E: SLC30A8 promoter DNA methylation levels in physical exercise intervention program in the youth subjects are not influenced by physical activity from the baseline to 3-months follow-up. SLC30A8: Solute carrier family 30 member 8; CON: Control, db/db mice without diabetic kidney disease; DKD: Diabetic kidney disease; PiPy: Physical exercise intervention program in the youth; T2D: Type 2 diabetes; SCA: Pancreatic serous cystadenoma.