Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease

BackgroundRevascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein （HDL） particle size （eHDL-S）, the ratio of HDL cholesterol （HDL-C） to apoprotein A-I （apoA-I）, is associated with the clinical outcomes of diabetic patients with stablecoronary artery disease （CAD）.MethodsWe per-formed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography. Patients were followed up for a mean duration of 12 months. The patients were divided into three groups by the tertiles of eHDL-S： low eHDL-S （〈 0.71,n= 118）; interme-diate eHDL-S （0.71-0.79,n= 111）; and high eHDL-S （〉 0.79,n= 99）. The associations between the baseline eHDL-S and short-term out-comes were evaluated using the Kaplan-Meier method and Cox proportional regression.Results The low eHDL-S group had higher trig-lyceride, hemoglobin A1c, uric acid, and leukocyte count than the other groups. During the follow-up period, 47/328 patients experienced a pre-specified outcome. According to the Kaplan-Meier analysis, the incidence of pre-specified outcomes was lower in the high eHDL-S group （P = 0.04）. However, eHDL-S was not independently associated with adverse outcomes in Cox proportional hazards regression （haz-ard ratio （HR）： 0.23, 95% confidence interval （95% CI）： 0.01-11.24,P = 0.493）.ConclusionAlthough the eHDL-S was associated with inflammatory biomarkers, it was not independently associated with the short-term prognosis of diabetic patients with stable CAD in the era of revascularization and potent statin therapy.

Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

Background Susceptibility to coronary artery disease （CAD） and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin Alc （HbAlo）, insulin, high-sensitivity C-reactive protein, tumor necrosis factor-a, and interleukin-6 were also measured, and compared with each patient＇s genotype. Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic （OR： 1.270, P=-0.044） and non-diabetic （OR： 1.369, P=0.011） patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics （P=0.019）, but not in non-diabetics （P=0.126）. Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD （OR：. 2.367, ,~=-0.008） and greater cumulative atherosclerotic burden compared with non-CC genotype carriers （Gensini score： 31.80＋17.20 vs. 23.09＋_21.63, P=-0.039）. No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbAlc, or inflammatory cytokines for diabetic or non-diabetic patients with CAD. Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.

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.