Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets.

With the pandemic of type 2 diabetes (T2D), there is an ever-increasing need to fully understand the underlying mechanisms of the disease. Type 2 diabetes shows a high heritability risk (25-80%); however, genes account only for 10% of this risk. From all the risk factors for diabetes, epigenetic mechanisms have the highest statistical scoring in explaining the disease. A multitude of organ-specific epigenomic changes have been linked to type 2 diabetes. Nutritional influences, mainly in the early life, physical activity level, environmental toxins act as epigenetic factors and the recognized epigenetic changes can represent a therapeutical target, new drugs being currently in development for this application. Our current review focuses on the most common epigenetic modifications linked to type 2 diabetes or insulin resistance, the potentially emerging epigenetic-related interventions and pharmacoepigenetic knowledge.

Genetic Approaches to the Study of Gene Variants and Their Impact on the Pathophysiology of Type 2 Diabetes.

Diabetes mellitus is an incurable progressive disease, characterized by elevated blood glucose levels, which lead to the development of micro- and macrovascular complications. Although the etiopathology of the disease remains unclear, it seems to be multifactorial, with an important interaction between genetics and environmental causes. Currently, the genetics of type 2 diabetes (T2D) is poorly understood. The recent advance of the genetic technologies and with a better understanding of genetics, more than 120 distinct genetic loci, with more than 150 variants, have been identified that may be involved in the pathogenesis of T2D. However, as these variants can account for only approximately 20% of the heritability of T2D, there is an obvious need for additional approaches to identify susceptibility genes or genetic mechanisms involved in the development of this disease. There is a growing number of genes found to be related to T2D; however, their individual impact on the pathogenesis of the disease appears to be low, while silencing of protective genes may also contribute to the development of this disease. The present review attempts to summarize our current knowledge in the field of genetics of T2D, highlighting the possible practical applications for each approach.

[Correlation of FABP2-A54T polymorphism and the metabolic syndrome in Maros County of Romania]. / A FABP2-A54T-polimorfizmus és a metabolikus szindróma kapcsolata a romániai Maros megyében.

OBJECTIVE: The FABP2 (intestinal fatty acid-binding protein) gene is expressed in the intestinal epithelial cells and codes for a protein involved in the fatty acid metabolism. We investigated the association of the A54T polymorphism of the FABP2 gene with the metabolic syndrome defined according to the diagnostic criteria recommended by the IDF in 2005, in our region (Marosvásárhely - Tg. Mures, Romania). RESEARCH DESIGN AND METHODS: A case-control study was carried out on 144 metabolic syndrome patients and 73 healthy persons with similar age and lifestyle. Insulin resistance was measured by the HOMA and QUICKI indices, and gene polymorphism was analyzed with PCR followed by restriction enzyme digestion with Hha I. RESULTS: The T54 allele was more frequent in the metabolic syndrome group than in controls (35.71% vs. 28.08%, p < 0.05). In the presence of the T54 allele we have noticed a slight but statistically significant risk, more marked in the case of TT homozygotes (TT vs. AT + AA: OR = 4.31, CI 95% 1.21-5.29, p = 0.015 and TT vs. AA: OR = 4.61, CI95%: 1.24-7.03, p = 0.0195). No significant differences of the followed metabolic parameters were observed between persons having different genotypes in the two study groups. CONCLUSIONS: These results suggest that the FABP2 T54 allele may have a minor contribution to the metabolic syndrome in our region.

[MLPA technique--principles and use in practice]. / Tehnica MLPA. Principii si utilitate practica.

MLPA (Multiplex Ligation-dependent Probe Amplification) is a recently introduced method, based on PCR principle, useful for the detection of different genetic abnormalities (aneuploidies, gene deletions/duplications, subtelomeric rearrangements, methylation status etc). The technique is simple, reliable and cheap. We present this method to discuss its importance for a modern genetic service and to underline its multiple advantages.