Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population.

Adaptor proteins containing PH domain, PTB domain, and leucine zipper motif 1 and 2 (APPL1/2) play a key role in cell proliferation in many tissues. APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine. This study aimed to investigate whether genetic variations in the APPL1/2 genes affect the risk of coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM). Seven haplotype-tagging single nucleotide polymorphisms (tag-SNPs) were selected from CHB HapMap database (Phase II) and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM, with the carriers of genotype CC at higher risk of CAD compared with non-carriers (OR = 2.830, 95%CI 1.285 - 6.230, P = 0.010; OR' = 4.992, 95%CI = 1.758 - 14.173, P' = 0.003, after adjustment for the other known CAD risk factors); the homozygotes of AA at rs11112412 in APPL2 gene had higher risk of CAD compared with those of GG (adjusted OR' = 5.697, 95%CI 1.006 - 32.257, P' = 0.049). Genetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population.