• DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1clevels: a systematic review and replication in a case-control sample of the Lifelines study.

      Walaszczyk, Eliza; Luijten, Mirjam; Spijkerman, Annemieke M W; Bonder, Marc J; Lutgers, Helen L; Snieder, Harold; Wolffenbuttel, Bruce H R; van Vliet-Ostaptchouk, Jana V (2018-02)
      Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1clevels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study.
    • The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients.

      Fraszczyk, Eliza; Luijten, Mirjam; Spijkerman, Annemieke M W; Snieder, Harold; Wackers, Paul F K; Bloks, Vincent W; Nicoletti, Carolina F; Nonino, Carla B; Crujeiras, Ana B; Buurman, Wim A; et al. (2020-01-20)
      To determine the impact of bariatric surgery and subsequent weight loss on clinical traits, a cohort of 40 severely obese individuals (BMI = 30-73 kg/m2) was examined at the time of surgery and at three follow-up visits, i.e., 3, 6, and 12 months after surgery. The majority of the individuals were women (65%) and the mean age at surgery was 45.1 ± 8.1 years. We observed a significant decrease over time in BMI, fasting glucose, HbA1c, HOMA-IR, insulin, total cholesterol, triglycerides, LDL and free fatty acids levels, and a significant small increase in HDL levels (all p values < 0.05). Epigenome-wide association analysis revealed 4857 differentially methylated CpG sites 12 months after surgery (at Bonferroni-corrected p value < 1.09 × 10-7). Including BMI change in the model decreased the number of significantly differentially methylated CpG sites by 51%. Gene set enrichment analysis identified overrepresentation of multiple processes including regulation of transcription, RNA metabolic, and biosynthetic processes in the cell. Bariatric surgery in severely obese patients resulted in a decrease in both biological age and epigenetic age acceleration (EAA) (mean = - 0.92, p value = 0.039).