Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration

Luigi Bouchard, Marie-France Hivert, Simon-Pierre Guay, Julie St-Pierre, Patrice Perron, Diane Brisson, Luigi Bouchard, Marie-France Hivert, Simon-Pierre Guay, Julie St-Pierre, Patrice Perron, Diane Brisson

Abstract

Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adiponectin gene (ADIPOQ) DNA methylation profile in placenta tissue, in maternal circulating blood cells, and in cord blood cells. We found that lower DNA methylation levels in the promoter of ADIPOQ on the fetal side of the placenta were correlated with higher maternal glucose levels during the second trimester of pregnancy (2-h glucose after the oral glucose tolerance test; r(s) ≤ -0.21, P < 0.05). Lower DNA methylation levels on the maternal side of the placenta were associated with higher insulin resistance index (homeostasis model assessment of insulin resistance) during the second and third trimesters of pregnancy (r(s) ≤ -0.27, P < 0.05). Finally, lower DNA methylation levels were associated with higher maternal circulating adiponectin levels throughout pregnancy (r(s) ≤ -0.26, P < 0.05). In conclusion, the ADIPOQ DNA methylation profile was associated with maternal glucose status and with maternal circulating adiponectin concentration. Because adiponectin is suspected to have insulin-sensitizing proprieties, these epigenetic adaptations have the potential to induce sustained glucose metabolism changes in the mother and offspring later in life.

Figures

FIG. 1.
FIG. 1.
Adiponectin (ADIPOQ) gene locus (chromosome 3q27). Numbers in the diamond shapes report Spearman correlation coefficients between CpG sites or linkage disequilibrium values (r2) between ADIPOQ SNPs, as computed with Haploview 4.0.
FIG. 2.
FIG. 2.
Spearman correlation between placental ADIPOQ gene promoter DNA methylation and 2-h post-OGTT glucose levels. Adjusted for weight gain between the first and third trimester (n = 98).
FIG. 3.
FIG. 3.
Spearman correlation between the fetal side of the placenta ADIPOQ gene promoter DNA methylation and maternal serum levels. Adjusted for the mother’s BMI at the first trimester and HOMA-IR at the second trimester. The results remained unchanged after the removal of the single outlier (n = 70).
FIG. 4.
FIG. 4.
Spearman correlation between the maternal side of the placenta ADIPOQ gene promoter DNA methylation and maternal serum levels. Adjusted for the mother’s BMI at the first trimester and HOMA-IR at the second trimester. The results remained unchanged after the removal of the single outlier (n = 70).
FIG. 5.
FIG. 5.
Fetal side of the placenta DNA methylation levels according to ADIPOQ genotypes.

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