Читать книгу Textbook of Lifestyle Medicine - Labros S. Sidossis - Страница 27

Genetic predisposition has been acknowledged to have a significant contribution to the incidence of NCDs. A number of mutations in the coding regions of the human genome have been considered as causative factors for various NCDs. Nonsynonymous nucleotide substitutions result in missense, nonsense, or frameshift changes in protein coding sequence; this may lead to loss‐of‐function or gain‐of‐function in certain proteins that have linked with specific disease phenotypes. However, the vast majority of single‐nucleotide polymorphisms (SNPs) are distributed throughout the human genome, in the noncoding regions. Therefore, it is difficult to establish a causal relationship between the allelic variants originating from SNPs and the disease phenotype.

The relationship between heritable genetic traits and metabolic morbidity has been accrued through genome‐wide association studies (GWASs), which examine similarities in the entire DNA sequence of different people, as regards specific SNPs, and the presence of certain diseases across this population. Data from GWASs have shown that SNPs are preferentially concentrated in functional genomic regions, namely enhancer elements, DNase hypersensitivity regions, and epigenetically important chromatin markers, playing a crucial role in the development of a variety of diseases, including cancer, stroke, and cerebrovascular diseases. Moreover, the epigenetic modifications in the form of DNA methylation lay among the most critical processes that could change gene expression, while at the same time leaving intact the nucleotide sequence (please refer to Chapter 3 for more information about the epigenetic mechanism).

FIGURE 2.1 Results of the Global Burden of Disease Collaborative Network, Global Burden of Disease Study 2017. Institute for Health Metrics and Evaluation (IHME) (2018).

FIGURE 2.2 Probability of dying from the four main noncommunicable diseases between the ages of 30 and 70 years, comparable estimates, 2012.

Source: Reprinted with permission from WHO Library Cataloguing‐in‐Publication Data Global Status Report on Noncommunicable Diseases, 2014 ed.

Diet, physical activity, sleep patterns, and stress have been shown to significantly affect the development of many NCDs. These factors can influence pathogenetic pathways and even gene expression, and therefore may positively or negatively affect the development of a disease. In the following paragraphs, we are presenting the epidemiology of the most important NCDs and the effect of the modern lifestyle. The protective role of several other lifestyle aspects in NCDs will be presented in Unit III.