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Distinct methylation patterns in genes that affect mitochondrial function are associated with kidney disease in blood‐derived DNA from individuals with Type 1 diabetes
Author(s) -
Swan E. J.,
Maxwell A. P.,
McKnight A. J.
Publication year - 2015
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.12775
Subject(s) - dna methylation , epigenetics , methylation , gene , type 2 diabetes , medicine , cytosine , genetics , biology , diabetes mellitus , endocrinology , gene expression
Abstract Aims Epigenetic modifications, such as DNA methylation, can influence the risk of developing kidney disease. We studied methylation profiles in genes related to mitochondrial function to assess whether differences in these epigenetic features were associated with diabetic kidney disease in people with Type 1 diabetes. Methods A case–control association study was undertaken ( n = 196 individuals with diabetic kidney disease vs. n = 246 individuals without renal disease). Participants were White and diagnosed with Type 1 diabetes before 31 years of age. Genes that encode mitochondrial proteins ( n = 780) were downloaded from mitoproteome.org. DNA methylation profiles from blood‐derived DNA were generated using the Illumina Infinium HumanMethylation450 (262 samples) and Illumina Infinium HumanMethylation27 (192 samples) arrays. Beta values (β) were calculated and quality control was conducted, including evaluating blind duplicate DNA samples. Results Fifty‐four Cytosine‐phosphate‐Guanine probes across 51 unique genes were significantly associated ( P ≤ 10 –8 ) with diabetic kidney disease across both the 450K and the 27K methylation arrays. A subanalysis, employing the 450K array, identified 755 Cytosine‐phosphate‐Guanine probes in 374 genes that were significantly associated ( P ≤ 10 ‐8 ) with end‐stage renal disease. Forty‐six of the top‐ranked variants for diabetic kidney disease were also identified as being differentially methylated in individuals with end‐stage renal disease. The largest change in methylation (Δβ = 0.2) was observed for cg03169527 in the TAMM 41 gene, chromosome 3p25.2. Three genes, PMPCB , TSFM and AUH , were observed with differential methylation at multiple Cytosine‐phosphate‐Guanine sites each ( P < 10 –12 ). Conclusions Differential methylation in genes that influence mitochondrial function are associated with kidney disease in individuals with Type 1 diabetes.