Differential methylation in inflammation and type 2 diabetes genes in siblings born before and after maternal bariatric surgery

OBJECTIVE: Siblings born before (BMS) and after (AMS) maternal biliopancreatic diversion (BPD) show differences in the methylome. The objective was to use a sibling-pair design to examine the effects from interpregnancy weight loss as a consequence of maternal bariatric surgery, other than BPD, on the methylome comparing BMS and AMS. METHODS: Women with at least one child born before and one after bariatric surgery were identified in Swedish national registers. Whole blood samples from BMS (N = 31) and AMS (N = 31) siblings were collected for epigenetic methylation analysis while maternal information was collected from antenatal medical records. RESULTS: In total 3,074 genes, with corresponding 23,449 CpG methylation sites, were differently methylated and associated with an overrepresentation of differently methylated CpG sites in genes involved with insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity, while the most significant differently methylated genes were HLA-DQA1, HLA-DQB1, and TSPAN18, when comparing BMS and AMS siblings. CONCLUSIONS: These results suggest that maternal bariatric surgery, with subsequent weight loss between pregnancies, is associated with alterations in the methylome of genes involved in insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity in a comparison of BMS and AMS siblings.