| Autor: |
Vohra, Manik, Adhikari, Prabha, Souza, Sydney C.D'., Nagri, Shivashankar K., Umakanth, Shashikiran, Satyamoorthy, Kapaettu, Rai, Padmalatha S. |
| Zdroj: |
Laboratory Investigation; August 2020, Vol. 100 Issue: 8 p1090-1101, 12p |
| Abstrakt: |
The interaction of genetic and epigenetic mechanisms is one of the underlying causes of phenotypic variability in complex diseases such as type 2 diabetes (T2D). To explore the influence of genetic and epigenetic changes in T2D, we examined the effect of methylation of CpG-SNP sites on allele-specific expression (ASE) in one-carbon metabolism pathway genes in T2D. Case-control study was conducted on 860 individuals (430 T2D and 430 controls). CpG-SNPs shortlisted through in silico analysis were genotyped using tetra ARMS PCR and validated using Sanger DNA sequencing. Global DNA methylation was carried out using RP-HPLC. Promoter DNA methylation and CpG site-specific methylation were carried out using bisulfite sequencing. mRNA expression and ASE were examined by SYBR green and TaqMan assay, respectively. Four exonic CpG-SNPs of MTHFD1, MTRR, and GGHgenes were identified in folate pathway genes. Among these, MTHFD1rs2236225 showed significant association with T2D independent of obesity, displayed ASE, and correlated with CpG-SNP site-specific methylation when compared with controls. Our results demonstrate that SNP rs2236225 in the CpG site of MTHFD1, which regulates allele-specific gene expression in PBMCs is methylation dependent and may perturb one-carbon metabolism pathway in T2D subjects. |
| Databáze: |
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