Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns
Abstract Background The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, h...
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BMC
2025-01-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-024-02568-6 |
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| author | Teresa M. Linares-Pineda Alfonso Lendínez-Jurado Alberto Piserra-López María Suárez-Arana María Pozo María Molina-Vega María José Picón-César Sonsoles Morcillo |
| author_facet | Teresa M. Linares-Pineda Alfonso Lendínez-Jurado Alberto Piserra-López María Suárez-Arana María Pozo María Molina-Vega María José Picón-César Sonsoles Morcillo |
| author_sort | Teresa M. Linares-Pineda |
| collection | DOAJ |
| description | Abstract Background The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements. Methods This study analyzed saliva DNA methylation patterns in 30 children (15 born to GDM mothers and 15 to non-GDM mothers) from the EPIDG cohort. Samples were collected at two time points: 8–10 weeks postpartum and at one year of age. Epigenome-wide analysis of over 850,000 CpG sites was conducted using the Illumina Methylation EPIC Bead Chip. Differential methylation positions (DMPs) were identified with the limma package, using a significance threshold of p < 0.01 and delta β ≥ 5%. Correlation analysis examined associations between methylation and growth variables (weight, height, BMI and annual growth) using Spearman tests. Results We identified 6,968 DMPs at the postpartum stage and 5,132 after one year, with 50 sites remaining differentially methylated over time, 16 of which maintained consistent methylation directionality. Functional analysis linked several of these DMPs to genes involved in inflammation and metabolic processes, including CYTH3 and FARP2, both implicated in growth and metabolic pathways. Significant correlations were found between specific CpG sites and growth-related variables such as weight, head circumference, height, and BMI. Conclusions This study’s longitudinal design reveals stable DNA methylation patterns in saliva samples that differentiate GDM-exposed children from controls across the first year of life, highlighting the feasibility of saliva as a minimally invasive biomarker source. The persistence of these epigenetic signatures underscores their potential as early indicators of metabolic risk, offering valuable insights into the long-term impact of maternal GDM on child health. Although the use of saliva offers a practical and non-invasive tool for pediatric epigenetic research, further studies are necessary to validate these findings in larger populations. |
| format | Article |
| id | doaj-art-91d4906dfa534f6bbf79fc6595d36a3f |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-91d4906dfa534f6bbf79fc6595d36a3f2025-01-19T12:09:06ZengBMCCardiovascular Diabetology1475-28402025-01-0124111010.1186/s12933-024-02568-6Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patternsTeresa M. Linares-Pineda0Alfonso Lendínez-Jurado1Alberto Piserra-López2María Suárez-Arana3María Pozo4María Molina-Vega5María José Picón-César6Sonsoles Morcillo7Department of Endocrinology and Nutrition, Virgen de la Victoria University HospitalBiomedical Research Institute-IBIMA Plataforma BIONANDDepartment of Cardiology, Virgen de la Victoria University HospitalDepartment of Obstetrics and Gynecology, Regional University Hospital of MálagaBiomedical Research Institute-IBIMA Plataforma BIONANDDepartment of Endocrinology and Nutrition, Virgen de la Victoria University HospitalDepartment of Endocrinology and Nutrition, Virgen de la Victoria University HospitalDepartment of Endocrinology and Nutrition, Virgen de la Victoria University HospitalAbstract Background The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements. Methods This study analyzed saliva DNA methylation patterns in 30 children (15 born to GDM mothers and 15 to non-GDM mothers) from the EPIDG cohort. Samples were collected at two time points: 8–10 weeks postpartum and at one year of age. Epigenome-wide analysis of over 850,000 CpG sites was conducted using the Illumina Methylation EPIC Bead Chip. Differential methylation positions (DMPs) were identified with the limma package, using a significance threshold of p < 0.01 and delta β ≥ 5%. Correlation analysis examined associations between methylation and growth variables (weight, height, BMI and annual growth) using Spearman tests. Results We identified 6,968 DMPs at the postpartum stage and 5,132 after one year, with 50 sites remaining differentially methylated over time, 16 of which maintained consistent methylation directionality. Functional analysis linked several of these DMPs to genes involved in inflammation and metabolic processes, including CYTH3 and FARP2, both implicated in growth and metabolic pathways. Significant correlations were found between specific CpG sites and growth-related variables such as weight, head circumference, height, and BMI. Conclusions This study’s longitudinal design reveals stable DNA methylation patterns in saliva samples that differentiate GDM-exposed children from controls across the first year of life, highlighting the feasibility of saliva as a minimally invasive biomarker source. The persistence of these epigenetic signatures underscores their potential as early indicators of metabolic risk, offering valuable insights into the long-term impact of maternal GDM on child health. Although the use of saliva offers a practical and non-invasive tool for pediatric epigenetic research, further studies are necessary to validate these findings in larger populations.https://doi.org/10.1186/s12933-024-02568-6Gestational diabetesOffspringEpigeneticDna methylationSalivaChild growth |
| spellingShingle | Teresa M. Linares-Pineda Alfonso Lendínez-Jurado Alberto Piserra-López María Suárez-Arana María Pozo María Molina-Vega María José Picón-César Sonsoles Morcillo Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns Cardiovascular Diabetology Gestational diabetes Offspring Epigenetic Dna methylation Saliva Child growth |
| title | Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns |
| title_full | Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns |
| title_fullStr | Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns |
| title_full_unstemmed | Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns |
| title_short | Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns |
| title_sort | longitudinal dna methylation profiles in saliva of offspring from mothers with gestational diabetes associations with early childhood growth patterns |
| topic | Gestational diabetes Offspring Epigenetic Dna methylation Saliva Child growth |
| url | https://doi.org/10.1186/s12933-024-02568-6 |
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