Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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 A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.</p><p><b>RESULTS</b>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, P = 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, HbA(1c), or inflammatory cytokines for diabetic or non-diabetic patients with CAD.</p><p><b>CONCLUSIONS</b>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.</p>

Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-beta1 expression and fibrosis in minipigs with ischemia-reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury.</p><p><b>METHODS</b>Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n = 5) or saline (control group, n = 5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-beta1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining.</p><p><b>RESULTS</b>As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 +/- 5.1) to (32.3 +/- 5.6) ml, P < 0.05) and end-systolic volume (from (8.3 +/- 3.2) to (15.2 +/- 4.1) ml, P< 0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 +/- 13.3)% to (50.2 +/- 11.9)%, P < 0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-beta1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P< 0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P < 0.05).</p><p><b>CONCLUSION</b>Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-beta1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.</p>

Association between the -1031T/C polymorphism in tumor necrosis factor-alpha gene and unstable angina / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between the -1031T/C polymorphism in the promoter of tumor necrosis factor-alpha (TNF- alpha) gene and unstable angina in Chinese Han population.</p><p><b>METHODS</b>The genotype of -1031T/C locus was analyzed by MALDI-TOF in 299 patients with unstable angina and 202 healthy controls. The serum TNF-alpha level was measured by enzyme-linked immunosorbent assay(ELISA).</p><p><b>RESULTS</b>There was no significant difference in the genotype distribution and allele frequencies of the -1031T/C locus between the two groups (P > 0.05). However, stratification by gender showed that the genotype distribution of this locus was obviously different between the two groups in men (P was 0.032). The risk of developing unstable angina in men carrying the CC+TC genotypes were 1.66-fold higher than that in men of TT genotype (95% CI: 1.040 to 2.659). There was no significant difference in the frequencies of the C and T alleles between the two subgroups (P > 0.05). Furthermore, serum TNF-alpha levels of the patients were significantly higher than those of controls (P = 0.028, P = 0.013 in men), but there was no significant difference in the TNF-alpha level among different genotypes.</p><p><b>CONCLUSION</b>The -1031T/C polymorphism of the TNF-alpha gene might be associated with unstable angina in male Han population, especially the C allele carriers might be more likely to be affected by unstable angina than the rest of the population.</p>