Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals

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dc.contributor.authorMatsha, Tandi E
dc.contributor.authorPheiffer, Carmen
dc.contributor.authorPheiffer, Carmen
dc.date.accessioned2021-10-08T07:04:26Z
dc.date.available2021-10-08T07:04:26Z
dc.date.issued2016
dc.description.abstractThe 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, and MTHFR rs1801133 and NOS3 rs1799983 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 (both ) and in screen-detected diabetes compared to known diabetes on treatment (). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (; 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 between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.
dc.identifier.apacitationMatsha, T. E., Pheiffer, C., & Pheiffer, C. (2016). Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals. <i>Journal of Diabetes Research</i>, 2016(4), 174 - 177. http://hdl.handle.net/11427/34506en_ZA
dc.identifier.chicagocitationMatsha, Tandi E, Carmen Pheiffer, and Carmen Pheiffer "Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals." <i>Journal of Diabetes Research</i> 2016, 4. (2016): 174 - 177. http://hdl.handle.net/11427/34506en_ZA
dc.identifier.citationMatsha, T.E., Pheiffer, C. & Pheiffer, C. 2016. Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals. <i>Journal of Diabetes Research.</i> 2016(4):174 - 177. http://hdl.handle.net/11427/34506en_ZA
dc.identifier.issn2314-6745
dc.identifier.issn2314-6753
dc.identifier.ris TY - Journal Article AU - Matsha, Tandi E AU - Pheiffer, Carmen AU - Pheiffer, Carmen AB - 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, and MTHFR rs1801133 and NOS3 rs1799983 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 (both ) and in screen-detected diabetes compared to known diabetes on treatment (). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (; 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 between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 4 J1 - Journal of Diabetes Research LK - https://open.uct.ac.za PY - 2016 SM - 2314-6745 SM - 2314-6753 T1 - Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals TI - Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals UR - http://hdl.handle.net/11427/34506 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34506
dc.identifier.vancouvercitationMatsha TE, Pheiffer C, Pheiffer C. Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals. Journal of Diabetes Research. 2016;2016(4):174 - 177. http://hdl.handle.net/11427/34506.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceJournal of Diabetes Research
dc.source.journalissue4
dc.source.journalvolume2016
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1155/2016/8738072
dc.subject.otherAdult
dc.subject.otherAfrican Continental Ancestry Group
dc.subject.otherAged
dc.subject.otherCross-Sectional Studies
dc.subject.otherDNA Methylation
dc.subject.otherDiabetes Mellitus, Type 2
dc.subject.otherFemale
dc.subject.otherGenetic Predisposition to Disease
dc.subject.otherGenotype
dc.subject.otherGlucose Intolerance
dc.subject.otherHumans
dc.subject.otherMale
dc.subject.otherMethylenetetrahydrofolate Reductase (NADPH2)
dc.subject.otherMiddle Aged
dc.subject.otherNitric Oxide Synthase Type III
dc.subject.otherPolymorphism, Single Nucleotide
dc.titleGlucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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