Klak Marta, Gomółka Magdalena, Kowalska Patrycja, Cichoń Justyna, Ambrożkiewicz Filip, Serwańska-Świętek Marta, Berman Andrzej, Wszoła Michał
Foundation for Research and Science Development, Warsaw, Poland.
Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Cent Eur J Immunol. 2020;45(4):439-453. doi: 10.5114/ceji.2020.103386. Epub 2021 Feb 7.
Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030. In 2015 American Diabetes Association (ADA) announced that 30.3 million Americans (that is 9.4% of the overall population) had diabetes of which only approximately 1.25 million had T1D. Nowadays, T1D represents roughly 10% of adult diabetes cases total. Multiple genetic abnormalities at different loci have been found to contribute to type 1 diabetes development. The analysis of genome-wide association studies (GWAS) of T1D has identified over 50 susceptible regions (and genes within these regions). Many of these regions are defined by single nucleotide polymorphisms (SNPs) but molecular mechanisms through which they increase or lower the risk of diabetes remain unknown. Genetic factors (in existence since birth) can be detected long before the emergence of immunological or clinical markers. Therefore, a comprehensive understanding of the multiple genetic factors underlying T1D is extremely important for further clinical trials and development of personalized medicine for diabetic patients. We present an overview of current studies and information about regions in the human genome associated with T1D. Moreover, we also put forward information about epigenetic modifications, non-coding RNAs and environmental factors involved in T1D development and onset.
1型糖尿病(T1D)是第三大常见的自身免疫性疾病,由遗传和环境风险因素引发。根据世界卫生组织(WHO)2014年的报告,各类糖尿病患者人数升至4.22亿,而1980年为1.08亿。据估算,到2030年底这一数字将翻倍。2015年,美国糖尿病协会(ADA)宣布,3030万美国人(占总人口的9.4%)患有糖尿病,其中只有约125万人患有T1D。如今,T1D约占成人糖尿病病例总数的10%。已发现不同基因座的多种遗传异常会导致1型糖尿病的发生。对T1D的全基因组关联研究(GWAS)分析已确定了50多个易感区域(以及这些区域内的基因)。这些区域中的许多由单核苷酸多态性(SNP)定义,但它们增加或降低糖尿病风险的分子机制仍不清楚。遗传因素(自出生就存在)早在免疫或临床标志物出现之前就能被检测到。因此,全面了解T1D潜在的多种遗传因素对于进一步开展临床试验以及为糖尿病患者开发个性化药物极为重要。我们概述了当前关于人类基因组中与T1D相关区域的研究和信息。此外,我们还提出了有关表观遗传修饰、非编码RNA以及参与T1D发生和发病的环境因素的信息。