[Recent advance in genetic marker for diabetic macroangiopathy]

Abstract

Because of Westernized life style, diabetes and its complications become one of the most popular diseases in Asian countries as well as Westernized countries. Compared with diabetic microvascular complications, several risk factors such as postprandial hyperglycemia, increased coagulability, chronic inflammation, and genetic risk factors may lead to augment atherosclerosis, are shown to result in diabetic macroangiopathies (acute coronary syndrome, brain infarction, and ASO). Addition to candidate gene approach, genome wide association study (GWAS) successfully elucidated several novel single nuclear polymorphisms (SNP), contributing atherosclerosis. However, these genetic risk factors are still shown to contribute a relatively small part of atherosclerosis. Recently we have determined more than 100 atherosclerosis-related SNPs of around 2,000 subjects with type 2 diabetes. We have shown the combination of two atherosclerosis-prone SNPs highly significantly contribute to carotid atherosclerosis and coronary artery disease in subjects with type 2 diabetes. Also, accumulation of oxygen stress-prone alleles of some SNPs are proven to relate with serum level of 8-OHdG, as oxidative stress marker, carotid IMT, and prevalence of old myocardial infarction. These data clearly indicate that several genetic risk factors as well as conventional risk factors additively or synergistically contribute to diabetic macroangiopathy.