Migration and DNA methylation: a comparison of methylation patterns in type 2 diabetes susceptibility genes between indians and europeans

Abstract

BackgroundType 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.MethodsQuantitative 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.ResultsConsistent 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 ADCY5rs17295401 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.ConclusionsAnalysis 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.

Differences in smoking associated DNA methylation patterns in South Asians and Europeans

“…We and others report differences in DNA methylation between South Asians and Europeans [13,14], though whether these are associated with smoking behaviour is unknown. Potential ethnic differences may be due to different smoking behaviours, or differences in molecular mechanisms which are important to identify and explore.…”

“…Previous research has almost exclusively been performed in European origin populations, and may not extrapolate to other ethnic groups, such as South Asians, where escalating rates of tobacco consumption will impact adversely on an already elevated susceptibility to cardio-metabolic disease [ 12 ]. We and others report differences in DNA methylation between South Asians and Europeans [ 13 , 14 ], though whether these are associated with smoking behaviour is unknown. Potential ethnic differences may be due to different smoking behaviours, or differences in molecular mechanisms which are important to identify and explore.…”

New insights from monogenic diabetes for “common” type 2 diabetes

“…For example, differential methylation has been observed in common loci like PPARG and IRS1 in adipose tissue from unrelated T2D patients compared with control individuals and expression of PDX1 and INS was decreased in pancreatic islets from diabetics compared to non-diabetic donors (Yang et al, 2011 , 2012 ). Interestingly, quantitative DNA methylation analysis also shows consistent differences in DNA methylation patterns between populations of different ethnicities at common loci KCNJ11 along with other loci like ADCY5 and FTO which are attributed to genetic and/or region-specific environmental factors (Elliott et al, 2013 ).…”

Type 2 diabetes is more closely associated with risk of colorectal cancer based on elevated DNA methylation levels of ADCY5

“…ADCY5 can affect glucose metabolism through glucose-coupled insulin secretion in human islets ( 16 ). Studies have shown that the levels of ADCY5 mRNA ( 17 ), methylation ( 12 ) and single nucleotide polymorphism ( 16 ) are closely related to T2DM, and the differences between different ethnic groups are consistent ( 16 ). Furthermore, ADCY3 of the same family is at present a promising target for anti-obesity therapeutics.…”