2. South Asia Network for Chronic Disease, Public Health Foundation of India, New Delhi, India.
3. Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.
4. University of Eastern Finland, Finland, and Kuopio University Hospital, Finland.
5. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
6. See Supplementary text.
7. Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
8. Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
9. MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social and Community Medicine, University of Bristol, Bristol, UK.
Background: Type 2 diabetes is a global problem that is increasingly prevalent in low and middle income countries including India, and is partly attributed to increased urbanisation. Genotype clearly plays a role in type 2 diabetes susceptibility. However, the role of DNA methylation and its interaction with genotype and metabolic measures is poorly understood. This study aimed to establish whether methylation patterns of type 2 diabetes genes differ between distinct Indian and European populations and/or change following rural to urban migration in India.
Methods: Quantitative DNA methylation analysis in Indians and Europeans using Sequenom® EpiTYPER® technology was undertaken in three genes: ADCY5, FTO and KCNJ11. Metabolic measures and genotype data were also analysed.
Results: Consistent differences in DNA methylation patterns were observed between Indian and European populations in ADCY5, FTO and KCNJ11. Associations were demonstrated between FTO rs9939609 and BMI and between ADCY5 rs17295401 and HDL levels in Europeans. However, these observations were not linked to local variation in DNA methylation levels. No differences in methylation patterns were observed in urban-dwelling migrants compared to their non-migrant rural-dwelling siblings in India.
Conclusions: Analysis of DNA methylation at three type 2 diabetes susceptibility loci highlighted geographical and ethnic differences in methylation patterns. These differences may be attributed to genetic and/or region-specific environmental factors.
Key words: Type 2 diabetes, DNA methylation, ethnicity