title: Glucose Tolerance,MTHFRC677T andNOS3G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals.
abstract: The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, andMTHFRrs1801133 andNOS3rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (bothp≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p= 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p> 0.999). In multivariable linear regression analysis, onlyNOS3was associated with increasing global DNA methylation (β= 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association betweenNOS3rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
authors.forename: Tandi E
authors.identifier: 0000-0001-7291-714X
authors.initials: TE
authors.lastname: Matsha
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa.
authors.forename: Carmen
authors.identifier: 0000-0002-0707-1552
authors.initials: C
authors.lastname: Pheiffer
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
authors.forename: Tinashe
authors.initials: T
authors.lastname: Mutize
authors.affiliation: Division of Chemical Pathology, Faculty of Medicine and Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa.
authors.forename: Rajiv T
authors.initials: RT
authors.lastname: Erasmus
authors.affiliation: Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Andre P
authors.identifier: 0000-0002-5183-131X
authors.initials: AP
authors.lastname: Kengne
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)