Miriam Rubio de Santos, I. Hadjiyianni, M. Perez-Nieves, D. Cao, J. Ivanova, T. Dilla, Juan José Gorgojo Martínez
Abstract Background: The real-world effectiveness of insulin therapy is influenced by poor treatment persistence. An international cross-sectional survey of people with type 2 diabetes mellitus (T2DM) was conducted to
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Pub Date : 2013-01-01Epub Date: 2013-02-06DOI: 10.7243/2050-0866-2-6
Hannah R Elliott, Gagandeep K Walia, Aparna Duggirala, Alix Groom, S Umakar Reddy, Giriraj R Chandak, Vipin Gupta, Markku Laakso, Jacqueline M Dekker, Mark Walker, Shah Ebrahim, George Davey Smith, Caroline L Relton
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 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.
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.
背景：2 型糖尿病是一个全球性问题，在包括印度在内的中低收入国家越来越普遍，部分原因是城市化进程加快。基因型显然在 2 型糖尿病易感性中起着作用。然而，人们对 DNA 甲基化的作用及其与基因型和代谢指标之间的相互作用却知之甚少。本研究旨在确定不同的印度和欧洲人群 2 型糖尿病基因的甲基化模式是否存在差异，以及/或在印度农村人口向城市迁移后是否发生变化：方法：使用 Sequenom® EpiTYPER® 技术对印度人和欧洲人的三个基因进行了 DNA 甲基化定量分析：ADCY5、FTO 和 KCNJ11。同时还分析了代谢指标和基因型数据：结果：在 ADCY5、FTO 和 KCNJ11 基因中，观察到印度人和欧洲人的 DNA 甲基化模式存在一致的差异。在欧洲人中，FTO rs9939609 与体重指数之间以及 ADCY5rs17295401 与高密度脂蛋白水平之间存在关联。然而，这些观察结果与 DNA 甲基化水平的局部变化无关。在印度，与居住在农村的非移民兄弟姐妹相比，居住在城市的移民的甲基化模式没有差异：结论：对三个 2 型糖尿病易感基因位点的 DNA 甲基化分析凸显了甲基化模式的地域和种族差异。这些差异可能归因于遗传和/或特定地区的环境因素。
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