慢性代谢性疾病的环境与遗传交互作用以及早期预防

Effects of environment and genetic interactions on chronic metabolic diseases

随着我国经济的发展和营养与生活方式的迅速变迁,近年来我国居民肥胖、2型糖尿病等慢性代谢性疾病患病率激增,已成为影响国民健康最主要的威胁。有研究显示:与白种人相比,亚洲人具有较高的2型糖尿病遗传易感性,这可能与"代谢性肥胖"表型和遭遇营养转型中的"致肥胖环境"有关。大量的研究结果表明,此类慢性代谢性疾病是遗传和环境因素交互作用的结果。随着全基因组关联研究开展,目前已发现了20多个肥胖和2型糖尿病易感基因,不仅揭示了不同种族人群在基因结构和效应值方面存在着差异,但同时也发现遗传方面的差异仍无法完全解释东西方人在发病风险方面的不同。膳食、生活方式等环境因素仍被认为是2型糖尿病发病中的重要决定因素。在全基因组关联研究后时代,国际上的研究将更加强调基因—基因、基因—环境、基因—表型之间的交互作用对代谢性疾病的影响和相关的机制。事实上,有研究表明,各种基因多态性、炎性因子和脂肪细胞因子等都可能成为早期诊断的生物标记物,而通过改变膳食和生活方式则是目前国际公认的预防和控制慢性代谢性疾病最有效的方法。然而,我国尤为缺乏在大规模前瞻性流行病学研究中对导致慢性代谢性疾病流行的主要遗传和环境因素,以及基因—环境相互作用对健康的影响方面的系统的研究。而这类研究将为建立适用于中国人群遗传和表型特征的早期诊断生物标记物和有效预防干预策略奠定基础。

Owing to rapid economic development and nutrition transition, obesity and type 2 diabetes epidemics have become one of major health challenges in China. Compared with western populations, Asian people are known to have higher genetic predisposition for type 2 diabetes, which may link to commonly observed ＂metabolically obese＂ phenotype and also encounter unhealthy diet and lifestyle associated obesogenic environment. It has been well established that these metabolic diseases are caused by a complex interplay of multiple genetic variants and environmental factors. With recent success of genome-wide association studies （GWAS）, approximately 20 loci have been discovered to be associated with the predisposition of obesity and type 2 diabetes. Although there are ethical differences regarding gene frequency and genetic effective size, which could not fully explain differences in the disease susceptibility. Therefore, lifestyle factors including dietary pattern, nutrients and physical activity are still considered as major determinants in the pathogenesis of type 2 diabetes and other metabolic diseases. In post GWAS era, the international trends in this research area will put more emphases on the interactions of gene-gene, gene-diet, and gene-phenotype. Existing studies have suggested that the genetic variants, inflammatory cytokines and adipocytokines could be used as predictive biomarkers in early diagnosis of chronic metabolic diseases. Meanwhile diet and lifestyle interventions have been internationally recoginized as the most effective strategy in controlling metabolic diseases. However, few large-scale prospective studies have been conducted in Chinese population to systematically investigate the effects of gene variants, environmental factors and their interaction on pathogenesis of chronic metabolic diseases. The evidence from these studies however would provide a solid scientific basis for establishing effective strategies which could be used in early diagnosis and disease prevention corresponding to Chinese genotype and phenotype.