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

摘要

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％ 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).Conclusion Genetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population.