Polymorphisms of the ATP-binding cassette sterol efflux transporter genes g5 and g8 in cardiovascular diseases and type 2 diabetes mellitus

Mutations with a decrease in the expression and function of the of the ATP-binding cassette genes proteins ABCG5 and ABCG8, as the main sterol efflux transporters, lead to the accumulation of xenosterols in plasma associated with changes in the lipid profile, hyperglycemia and the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2). The review presents studies of the role of ABCG5/G8 polymorphisms in CVD and DM2. In several studies, including large–scale ones, the influence of ABCG5/G8 variants (rs4245791, rs41360247 rs4299376, rs11887534, rs7598542, rs78451356, etc.) on the risk of coronary heart disease (CHD) was proved, in others – when confirming the association of the risk of CHD with ABCG5 polymorphism, this status for ABCG8 was denied. Since sterol metabolism disorders observed in individuals with DM2 are probably associated with low insulin sensitivity, many authors confirmed the association of variants rs4299376, rs4148211, rs140231607 and rs6720173 of the ABCG5/G8 with the risk of DM2, but some authors did not find such a connection with DM2 for variants rs4299376, rs11887534 and rs4148217 of the ABCG8. A decrease in ABCG5/G8 mRNA expression was observed in DM2 in experimental animals and in humans; on the contrary, overexpression of ABCG5/G8 in db/db mice restored the sensitivity of the liver to insulin, which led to a decrease in fasting glucose, lipids and improved glucose tolerance. The inconsistency of data on the association of ABCG5/G8 gene polymorphism with the risk of CVD and DM2 may probably be due to inter-population differences, which necessitates further study of the contribution of ABCG5/G8 variants to the risk of these diseases.

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