RESUMO
The development of myopia is influenced by multiple environmental and genetic factors. A third component, epigenetics, may shed light on some of the relationships between environmental and genetic factors. Epigenetics is defined as the study of modulations of gene activity that can be transmitted over cell divisions without involving mutation of the DNA sequence. Methylation is one of the main mechanisms by which gene expression is decreased. In the context of myopia, the study of epigenetic mechanisms also contributes to the understanding of the involvement of candidate genetic variants. The analysis of metabolic and signalling pathways associated with ocular development enables discussion of the biological significance associated with these candidate genes. A better understanding of epigenetic mechanisms would allow individual risk estimations for myopia and probably targeting of therapeutic interventions at a population level. Measuring the level of DNA methylation at candidate gene sites could be used to monitor the effectiveness of myopia prevention measures such as reducing near work and increasing outdoor activity. More specifically, one could consider activating the methylation of myopia promoter genes or, on the contrary, inhibiting the methylation of myopia repressor genes. Finally, the control of metabolic and signalling pathways could be considered by targeting, for example, the regulation of the G protein signalling pathway (RGS 2) with the expression of the adenosine A2a receptor (AdoRs).
Assuntos
Epigênese Genética , Miopia , Humanos , Miopia/genética , Miopia/terapiaRESUMO
Age-related macular degeneration (AMD) is a complex multifactorial condition involving multiple genetic, environmental and constitutional factors. Inflammation, oxidative stress and lipid metabolism seem to be the most important factors in the pathogenesis of the disease. The importance of genetic factors has mainly been revealed with the influence of histocompatibility complement factor H (CFH) variations and the ARSM2 susceptibility gene. Another component, epigenetics, could help to explain some of the relationships between environmental and genetic factors. Epigenetics is defined as the study of modulations of gene activity that can be transmitted over cell divisions without involving mutation of the DNA sequence. The molecules that are involved in these mechanisms are referred to as the epigenome. The mechanisms involve DNA methylation, histone modification, chromatin remodeling, and gene inhibition by non-coding RNA. Epigenetics could explain how the environment may induce relatively stable changes in traits or even diseases, possibly inheritable over several generations. Epigenetic traits established during development, and/or acquired under the influence of nutritional factors or other environmental factors, could influence the interactions between genes and the environment. Several authors have recently shown the influence of epigenetic factors in the pathogenesis of ocular diseases such as cataract, dry eye, glaucoma, diabetic retinopathy and more recently AMD. A better understanding of the involvement of genetic variants at risk, their relationship with epigenetics and environmental factors would certainly help to better assess the risk of developing AMD or better understand recent changes in the incidence of the disease.
Assuntos
Epigênese Genética/fisiologia , Degeneração Macular/genética , Fator H do Complemento/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Degeneração Macular/patologiaRESUMO
The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.