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

Background 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 APPL 1/2 genes affect the risk of coronary artery disease （CAD） in Chinese patients with type 2 diabetes mellitus （T2DM）. Methods 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. Results 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% Cl 1.285-6.230, P=0.010; OR＇=4.992, 95% C1=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 OFt=5.697, 95% Cl 1.006-32.257, P=0.049）. Conclusion Genetic variation（s） in APPL 1/2 may be associated with CAD risk in T2DM in Chinese population.