Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians.

BACKGROUND

Leptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a "thin-fat-phenotype".

OBJECTIVE

Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene () DNA methylation.

METHODS

We performed DNA methylation analyses of 13 placental CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.

RESULTS

South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p<0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p<0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.

CONCLUSIONS

Maternal glucose and lipid metabolism is related to placental methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.