Diabetologie und Stoffwechsel 2014; 9 - FV58
DOI: 10.1055/s-0034-1374915

Promoter methylation of TMEM18 in subcutaneous adipose tissue is related to glucose homeostasis

K Rohde 1, 2, M Keller 1, M Klös 1, D Schleinitz 1, A Dietrich 3, MR Schön 4, D Gärtner 4, T Lohmann 5, M Dreßler 5, M Stumvoll 1, 2, P Kovacs 1, M Blüher 2, Y Böttcher 1
  • 1IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
  • 2Department of Medicine, University of Leipzig, Leipzig, Germany
  • 3Department of Surgery, University of Leipzig, Leipzig, Germany
  • 4Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, Germany
  • 5Municipal Clinic Dresden-Neustadt, Dresden, Germany

Context: Epigenetic processes such as dynamic promoter methylation may play a role in obesity, fat distribution and its accompanied metabolic alterations. TMEM18 is a candidate gene for BMI comprising the second largest effect size among all loci identified so far via GWAS.

Objective: We hypothesized that differential TMEM18 gene expression in visceral (VAT) and subcutaneous adipose tissue (SAT) may be a consequence of depot specific differential methylation at the TMEM18 promoter region. Differential methylation levels may confer fat depot specific correlations with measures of obesity and fat distribution.

Design and Methods:

(i) TMEM18 mRNA expression was measured in VAT and SAT from 511 subjects.

(ii) We investigated 50 Caucasian individuals for differential methylation levels in VAT vs. SAT at three CpG sites.

(iii) Subsequently, we tested for potential correlation of these methylation levels with anthropometric and metabolic parameters.

Results:

(i) In 511 individuals, we observed significantly decreased mRNA expression in SAT (paired t-test, P < 0.0001) compared to VAT.

(ii) We identified significantly higher methylation levels for the entire CpG locus in SAT (t-test, P = 0.007).

(ii) In lean individuals, we detected strong correlations between CpG methylation levels in SAT with parameters of fat distribution (visceral fat area, r = 0.581; P = 0.003) and with metabolic traits (p ≤0.05). After accounting for multiple testing, HbA1c and fasting plasma glucose remained statistically significant correlates of TMEM18 methylation (P = 2 × 10-4; P = 0.011, respectively) (iii).

Conclusions: Our data suggest that adipose tissue specific methylation may influence individual variability in glucose homeostasis independently of obesity, probably via altered TMEM18 mRNA expression.