Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Study Participants
2.2. Genome-Wide DNA Methylation Profiling
2.3. Functional Enrichment Analysis
3. Discussion
4. Materials and Methods
4.1. Study Participants
4.2. DNA Extraction
4.3. Genome-Wide DNA Methylation Profiling
4.4. Processing and Analysis of the Human Methylation EPIC Bead Chip Array
4.5. Functional Enrichment Analysis
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
GDM | Gestational diabetes mellitus |
CAMTA1 | Calmodulin binding transcription activator 1 |
MAPK | Mitogen activated protein kinase |
PI3K | Phosphoinositide 3-kinase |
T2D | Type 2 diabetes |
CpG | Cytosine-phosphate-guanine |
OGTT | Oral glucose tolerance test |
HIV | Human immunodeficiency virus |
BMI | Body mass index |
HOMA | Homeostatic model of assessment |
CRP | c-Reactive protein |
HbA1c | Glycated hemoglobin |
PCA | Principal component analysis |
FDR | False discovery rate |
UTR | Untranslated regions |
CDS | Coding domain sequences |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
GO | Gene Ontology |
NRG1 | Neuregulin 1 |
SNIP1 | smad Nuclear Interacting Protein 1 |
PPFIBP2 | Protein-tyrosine phosphatase, receptor-type, f polypeptide-interacting protein-binding protein 2 |
SWAP70 | Switching b cell complex subunit swap70 |
SEMA6D | Semiphorin 6d |
CDH8 | Cadherin 8 |
WNT6 | Wnt family member 6 |
RFTN1 | Raftlin, lipid raft linker 1 |
UNC5C | Unc-5 netrin receptor c |
NUDT6 | Nucleoside diphosphate-linked moiety x motif 6 |
STOX2 | Storkhead box |
MSH5 | Muts protein homolog 5 |
KHDRBS2 | KH RNA binding domain containing, signal transduction associated 2 |
NRG1 | Neuregulin 1 |
SLC9A3 | Solute carrier family 9 member a3 |
MEA1 | Male-enhanced antigen 1 |
KLHDC3 | Kelch domain-containing protein 3 |
RASA3 | RAS p21 protein activator 3 |
CYP26B1 | Cytochrome p450 family 26 subfamily b member 1 |
IADPSG | International association of diabetes in pregnancy study group |
WHO | World Health Organisation |
HAPO | Hyperglycemia and adverse pregnancy outcomes |
T1D | Type 1 diabetes |
EDTA | Ethylenediaminetetraacetic acid |
NOOB | Normal-exponential out-of-band |
SEM | Standard error of the mean |
ANOVA | One-way analysis of variance |
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Variables | Non-GDM (n = 12) | GDM (n = 12) | p-Value | |
---|---|---|---|---|
Age (years) a | 27.3 (0.3) | 27.3 (0.3) | 1.00 | |
Gestational age (weeks) a | 19.3 (1.5) | 19.3 (2.0) | 1.00 | |
BMI (kg/m2) a | 27.1 (1.3) | 27.6 (1.1) | 0.77 | |
Fasting glucose (mmol/L) a | 4.3 (0.1) | 5.5 (0.1) | <0.001 | |
1hr OGTT (mmol/L) a | 5.2 (0.3) | 6.6 (0.4) | 0.01 | |
2hr OGTT (mmol/L) a | 5.2 (0.3) | 5.8 (0.3) | 0.07 | |
HbA1c (%) a | 5.1 (0.1) | 5.1 (0.1) | 0.85 | |
Fasting insulin (mIU/L) b | 8 (7.5-9.0) | 10.2 (6.3-12.7) | 0.65 | |
HOMA b | 1.6 (1.6-1.8) | 2.6 (1.5-2.9) | 0.31 | |
Adiponectin (µg/mL) b | 10.4 (7.3-23.8) | 9.7 (4.7-12.0) | 0.28 | |
C-reactive protein (mg/L) a | 7.1 (1.2) | 7.7 (1.1) | 0.75 | |
Risk factors: n (%) c | None | 10 (83.3) | 7 (58.3) | 0.37 |
≥1 risk factor | 2 (16.7) | 5 (41.8) | ||
* Education: n (%) c | <grade 12 | 7 (63.6) | 5 (41.7) | 0.29 |
≥grade 12 | 4 (36.4) | 7 (58.3) | ||
Employment: n (%) c | None | 8 (66.7) | 7 (58.3) | 1.00 |
Formal/informal employment | 4 (33.3) | 5 (41.7) |
Probe ID | Location | Gene Symbol | Gene Name | Region | p-Value | Methylation |
---|---|---|---|---|---|---|
cg22985016 | Chr5:492187–524227 | SLC9A3 | Solute Carrier Family 9 Member A3 | Intron | 1.84 × 10−7 | ↑ |
cg21910650 | Chr6:42976841–42986722 | MEA1; KLHDC3 | Male-Enhanced Antigen 1; Kelch domain-containing protein 3 | Promoter/5’UTR | 3.23 × 10−6 | ↓ |
g23643951 | Chr1:7151432–7309551 | CAMTA1 | Calmodulin Binding Transcription Activator 1 | Intron | 4.46 × 10−6 | ↓ |
cg16306629 | Chr8:119121060–119129059 | COLECT10 * | Collectin Subfamily member 10* | Enhancer * | 9.22 × 10−6 | ↑ |
07966372 | Chr13:114782770–114898099 | RASA3 | RAS P21 Protein Activator 3 | 5’UTR/Intron | 9.75 × 10−6 | ↓ |
CpG Site | a Univariate | b Multivariate | ||||
---|---|---|---|---|---|---|
Coefficient | 95% CI | p-Value | Coefficient | 95% CI | p-Value | |
cg22985016 (SLC93A) | 0.028 | 0.019; 0.037 | <0.001 | 0.028 | 0.019; 0.037 | <0.001 |
cg21910650 (MEA1;KLHDC3) | −0.088 | −0.117; −0.058 | <0.001 | −0.087 | −0.118; −0.056 | <0.001 |
cg23643951 (CAMTA1) | −0.056 | −0.070; −0.042 | <0.001 | −0.056 | −0.071; −0.042 | <0.001 |
cg16306629 (Unknown) | 0.274 | 0.183; 0.366 | <0.001 | 0.275 | 0.192; 0.359 | <0.001 |
cg07966372 (RASA3) | −0.015 | −0.025; −0.004 | 0.006 | −0.015 | −0.026; −0.004 | 0.008 |
Variable | cg22985016 (SLC93A) | cg21910650 (MEA1; KLHDC3) | cg23643951 (CAMTA1) | cg16306629 (Unknown) | cg07966372 (RASA3) | |||||
---|---|---|---|---|---|---|---|---|---|---|
Rho | p-Value | Rho | p-Value | Rho | p-Value | Rho | p-Value | Rho | p-Value | |
Fasting glucose (mmol/L) | 0.728 | <0.001 | −0.694 | <0.001 | −0.735 | <0.001 | 0.724 | <0.001 | −0.452 | 0.026 |
1 h OGTT (mmol/L) | 0.502 | 0.012 | −0.377 | 0.069 | −0.399 | 0.053 | 0.559 | 0.004 | 0.016 | 0.939 |
2 h OGTT (mmol/L) | 0.297 | 0.168 | −0.249 | 0.250 | −0.338 | 0.115 | 0.266 | 0.219 | 0.098 | 0.658 |
Fasting insulin (mIU/L) | −0.037 | 0.888 | −0.103 | 0.691 | −0.204 | 0.433 | 0.109 | 0.674 | −0.495 | 0.043 |
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Dias, S.; Adam, S.; Rheeder, P.; Louw, J.; Pheiffer, C. Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 5828. https://doi.org/10.3390/ijms20235828
Dias S, Adam S, Rheeder P, Louw J, Pheiffer C. Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus. International Journal of Molecular Sciences. 2019; 20(23):5828. https://doi.org/10.3390/ijms20235828
Chicago/Turabian StyleDias, Stephanie, Sumaiya Adam, Paul Rheeder, Johan Louw, and Carmen Pheiffer. 2019. "Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus" International Journal of Molecular Sciences 20, no. 23: 5828. https://doi.org/10.3390/ijms20235828