Adiponectin Levels And Promoter Gene Polymorphisms Are Associated With The Protection Of Coronary Atheroslcerosis

Objective:To investigate the association of adiponectin protein isoforms and promoter polymorphism with coronary atherosclerosis in early-onset coronary artery disease population.Methods:According to age (male≤=55, female≤65), ECG and coronary angiography results, EOCAD group (382 cases) and control group (305 cases) were enrolled into the present study. Severity of coronary atherosclerosis was evaluated by Gensini score. Detailed archives were set up for all the patients, including general information, demographics, personal history, family history, medication history, and biochemical indicators. Serum levels adiponectin protein isoforms were measured by enzyme-linked immunosorbent assay (ELISA). After genomic DNA was extracted with Hipure Blood DNA Kits, sequencing and genotyping the three loci rs16861194(-11426A/G), rs17300539(-11391G/A) and rs266729(-11377C/G) in the promoter region of adiponectin gene.Results:Total adiponectin, high-molecular weight (HMW) adiponectin and H/T (HMW-total ratio) were significantly lower in EOCAD group compared to control group. Spearman correlation analysis indicated that HMW adiponectin and H/T were positively associated with CAD onset age, and negatively associated with atherosclerotic severity, which was stronger than that of total adiponectin. Binary logistic regression analysis demonstrated that HMW adiponectin and H/T were independent protective factor for coronary atherosclerosis. ORs were 0.234 and 0.138 separately (P<0.05). ROC curve indicated that areas under the ROC curves of HMW adiponectin and H/T were larger than that of total adiponectin, which were more effective biomarkers for CAD risk. There were no significant differences of genotype and allele frequencies in-11426 A/G locus between control and EOCAD group. All the genotypes in-11391G/A locus were wild type, while mutant and heterozygous type were failed to detect in this study population. In the-11377 locus, genotype GG, CG and allele G of EOCAD group were significantly higher than those of control group. Genotype GG was significantly associated with lower adiponectin levels, and could significantly increase the CAD risk (OR=1.361, P=0.032). Haplotype AGG was independently associated with CAD risk (OR= 1.646, P=0.038).Conslusions:1) Serum adiponectin levels were negatively correlated with the severity of coronary atherosclerosis, exerting an anti-atherosclerosis cardioprotective effect.2) HMW adiponectin and H/T are independent protective factors for coronary atherosclerosis and more effective biomarkers for the risk of CAD than total adiponectin.3) Mutation in -11377C/G locus of adiponectin promoter region was negatively associated with lower adiponectin levels, and could increase the risk of CAD. Haplotype AGG was an independently risk factor for coronary atherosclerosis.