Article

Promoter Polymorphism of Interleukin18 in Angiographically Proven Coronary Artery Disease

Department of Cardiology, Xiangfan Central Hospital, Xiangfan, Hubei, China.
Angiology (Impact Factor: 2.37). 04/2009; 60(2):180-185. DOI: 10.1177/0003319708319939

ABSTRACT Interleukin 18 (IL-18) is a pro-atherogenic cytokine associated with the occurrence of various cardiac complications. The IL-18 gene has a functional -137 G/C polymorphism (rs187238) in the promoter region. Using the ligase detection reaction-polymerase chain reaction, we genotyped a cohort of patients in Chinese Han population in Xiangfan region. Case patients of coronary artery disease and control patients were identified by coronary angiography. The plasma IL-18 concentrations were measured by ELISA. A significant increase of G allele or GG-genotype was observed in 241 case patients compared to 145 control individuals (frequency of G allele = 0.90 vs 0.83, p=0.004; frequency of GG-genotype = 0.81 vs 0.68, p = 0.005). In case patients, G allele carriers in multi-vessel disease patients had a higher occurrence rate when compared to single-vessel disease patients, but no significant difference was detected (frequency of G allele = 0.92 vs 0.88, p=0.107; frequency of GG-genotype = 0.84 vs 0.75, p = 0.089). IL-18 protein concentration of the -137GG genotype was much higher than concentration of the CG and CC genotype (case patients: 229.1±131.5 vs 122.7±73.6 pg/ml, P < 0.001; control patients: 65.9±31.6 vs 42.4±19.5 pg/ml, P < 0.001). To conclude, IL-18 promoter -137G/C polymorphism influences IL-18 levels and the occurrence of coronary artery disease, suggesting that IL-18 is causally involved in the development of atherosclerosis.

0 Followers
 · 
57 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the -607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the -607C/A (rs1946518) polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 -137G/C (rs187238) polymorphism and the -13T/C (rs11024595) polymorphism in the 5'-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele (C homozygotes) was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the -13T/C (rs11024595) polymorphism in the 5'-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the -607C/A (rs1946518) polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.
    Neural Regeneration Research 07/2013; 8(20):1881-91. DOI:10.3969/j.issn.1673-5374.2013.20.007 · 0.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 2 diabetes is a major risk factor for myocardial infarction (MI) and chronic inflammation may play a central role in both diseases. Interleukin (IL)-18 is a potent proinflammatory cytokine, which is considered important in acute coronary syndromes and type 2 diabetes. We investigated the association of the -137 (G>C), polymorphism (rs187238) and the -607 (C>A) polymorphism (rs1946518) of the IL-18 gene promoter region in 495 Caucasians with type 2 diabetes, of whom 169 had MI and 326 subjects had no clinically evident coronary artery disease (controls). We also investigated the impact of these polymorphisms on the serum IL-18 level in subsets of both groups and in a normal group. Genotype distributions of the polymorphisms showed no significant difference between cases and controls. However, IL-18 serum levels were significantly lower in diabetics with the 137 CC genotype than in those with other genotypes (241.5 ± 132.7 ng/L vs. 340.2 ± 167.4 ng/L; p <0.05). High sensitivity C-reactive protein and IL-18 serum levels were higher in diabetics in the MI group than in the control group. We conclude that these IL-18 promoter gene polymorphisms are not risk factors for MI in Caucasians with type 2 diabetes.
    Balkan Journal of Medical Genetics 06/2011; 14(1):3-9. DOI:10.2478/v10034-011-0011-6 · 0.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We conducted a case-control study with 322 cases and 322 controls to assess the role of the two common SNPs in the promoter of IL-18 gene. Polymerase chain reaction restriction fragment length of polymorphism (PCR-RFLP) was taken to genotype -607A/C and -137C/G in the promoter of the IL-18 gene. By comparing cases and control subjects, we found that IS cases were more likely to have higher BMI, higher proportion of hypertension, and have higher proportion of smokers and drinkers. We found that IL-18 -607CC genotype (OR=1.70, 95% CI=1.03-2.81) and C allele (OR=1.26, 95% CI=1.01-1.58) were significantly more frequent in IS patients when compared with AA genotype. We did not find significant association between IL-18 -607A/C gene polymorphism and BMI, hypertension, smoking and drinking on the risk of IS. Our study suggests that polymorphisms in IL-18 -607A/C can influence the development of IS, and this gene polymorphism is associated with risk of IS in a Chinese population.
    Pakistan Journal of Medical Sciences Online 01/2015; 31(1):198-202. DOI:10.12669/pjms.311.5997 · 0.10 Impact Factor