Association of maternal and fetal LEPR common variants with maternal glycemic traits during pregnancy

Abstract

Recent studies suggested that maternal and placental leptin receptor (LEPR) may be involved in maternal glucose metabolism in pregnancy. To identify maternal and fetal LEPR common variants influencing gestational glycemic traits, we performed association study of 24-28-week maternal fasting glucose, glucose 1 hour after the consumption of a 50-g oral glucose load, fasting insulin and indices of beta-cell function (HOMA-β) and insulin resistance (HOMA-IR) in 1,112 unrelated women and their children. Follow-up of 36 LEPR loci identified 3 maternal loci (rs10889567, rs1137101 and rs3762274) associated with fasting glucose, these 3 fetal loci associated with fasting insulin and HOMA1-IR, as well as these 3 maternal-fetal loci combinations associated with HOMA2-β. We also demonstrated association of maternal locus rs7554485 with HOMA2-β and HOMA2-IR, maternal locus rs10749754 with fasting glucose, fetal locus rs10749754 with HOMA2-IR. However, these associations were no longer statistically significant after Bonferroni correction. In conclusion, our results first revealed multiple associations between maternal and fetal LEPR common variants and gestational glycemic traits. These associations did not survive Bonferroni correction. These corrections are overly conservative for association studies. We therefore believe the influence of these nominally significant variants on gestational glycometabolism will be confirmed by additional studies.

Crosstalk between genetic variability of adiponectin and leptin, glucose‐insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14

“…This might reflect a sort of compensatory regulation between insulin sensitivity/secretion and leptin regulation; indeed, the crosstalk between leptin receptor and insulin resistance has already been documented in other studies 53,54 . As mentioned above, the link between the genetic variants of the LEPR gene, insulin resistance and obesity were confirmed in both children and adults with or without diabetes 55–57 . As expected, our results, coherently with those from former studies, suggest the existence of a leptin receptor resistance that could lead to an alteration of the hormonal feedback, thus causing an increased production of proinflammatory markers at the endothelial level and a concomitant reduction of insulin sensitivity.…”

Leptin receptor mediates the proliferation and glucose metabolism of pancreatic cancer cells via AKT pathway activation

“…It has been reported that LepR can trigger the activation of several pathways, including Pi3K/aKT and Janus-activated kinase/STaT (18)(19)(20). lepr common variant (lepr-common) is reported to influence gestation glycemic traits (21). Leptin is highly expressed in subsets of cancer patients including breast, colon and prostate cancer, and stimulates various biological activities in cancer cells, including cell proliferation, migration and invasion (22)(23)(24)(25).…”