PMID- 30345607 OWN - NLM STAT- Publisher LR - 20240227 IS - 1742-1241 (Electronic) IS - 1368-5031 (Linking) DP - 2018 Oct 21 TI - Assessment of global long interspersed nucleotide element-1 (LINE-1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2DM) individuals. PG - e13270 LID - 10.1111/ijcp.13270 [doi] AB - INTRODUCTION: Recent studies have indicated that methylation of the LINE-1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE-1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. METHODS: A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE-1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. RESULTS: The overall mean +/- SD global LINE-1 methylation was 75.81 +/- 3.25%. Cross-sectional linear regression analysis at baseline year 2002 showed that LINE-1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient beta = -0.25), estimated glomerular filtration rate (eGFR) (beta = -0.48) and cholesterol HDL ratio (beta = -0.04). A 10% increase in LINE-1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m(2) and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14-year-follow-up periods showed that global LINE-1 methylation at baseline was associated with lower BMI in women [beta = -0.25] and lower cholesterol: HDL ratio [beta = -0.07]. A 10% increase in LINE-1 methylation was associated with reduction in BMI by 2.5 kg/m(2) in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. CONCLUSION: In a 14-year longitudinal cohort of T2DM individuals, relations between global LINE-1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Malipatil, Nagaraj AU - Malipatil N AD - The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Lunt, Mark AU - Lunt M AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Narayanan, Ram Prakash AU - Narayanan RP AD - Institute for Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK. FAU - Siddals, Kirk AU - Siddals K AD - The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Cortes Moreno, Gabriela Y AU - Cortes Moreno GY AD - High Speciality Regional Hospital of Ixtapaluca, Mexico City, Mexico. FAU - Gibson, Martin J AU - Gibson MJ AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. AD - NorthWest EHealth Ltd, Manchester, UK. FAU - Gu, Harvest F AU - Gu HF AD - Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden. FAU - Heald, Adrian H AU - Heald AH AUID- ORCID: 0000-0002-9537-4050 AD - The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Donn, Rachelle P AU - Donn RP AD - The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. LA - eng PT - Journal Article DEP - 20181021 PL - India TA - Int J Clin Pract JT - International journal of clinical practice JID - 9712381 EDAT- 2018/10/23 06:00 MHDA- 2018/10/23 06:00 CRDT- 2018/10/23 06:00 PHST- 2018/04/15 00:00 [received] PHST- 2018/09/06 00:00 [accepted] PHST- 2018/10/23 06:00 [entrez] PHST- 2018/10/23 06:00 [pubmed] PHST- 2018/10/23 06:00 [medline] AID - 10.1111/ijcp.13270 [doi] PST - aheadofprint SO - Int J Clin Pract. 2018 Oct 21:e13270. doi: 10.1111/ijcp.13270.