LPA kringle IV type 2 is associated with type 2 diabetes in a Chinese population with very high cardiovascular risk

Abstract

The connection between lipoprotein (a) [Lp(a)] levels and the risks of cardiovascular disease and diabetes remains poorly understood. Lp(a) is encoded by the LPA gene, and evidence suggests that the kringle IV type 2 (KIV-2) variant is particularly important to Lp(a) isoform size. A large isoform size, represented as a high number of KIV-2 repeats in LPA, is associated with low serum Lp(a) concentrations and an increased risk of type 2 diabetes. We investigated the associations among Lp(a) concentrations, LPA KIV-2 repeats, and type 2 diabetes in a Chinese population of 1,863 consecutive patients with very high cardiovascular risk, as identified by coronary angiography. Individuals with Lp(a) levels in the top tertile [67.86 (35.34–318.50) mg/dl] had a lower risk of diabetes compared with those in the bottom tertile [7.38 (0.60–12.91) mg/dl]. There was an inverse association between the number of KIV-2 repeats and serum Lp(a) concentrations. This study demonstrated that a high number of LPA KIV-2 repeats are associated with increased risk of type 2 diabetes in a Chinese population with very high cardiovascular risk, which suggests that large Lp(a) isoform size, associated with low Lp(a) concentration, has a causal effect on type 2 diabetes.