IL-8 -251A/T polymorphism contributes to coronary artery disease susceptibility in a Chinese population

BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients.OBJECTIVETo investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients.DESIGNCase-control study.SETTINGTertiary care center, Riyadh.METHODSTwo hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis.MAIN OUTCOME MEASUREThe strength of association between the Q192R polymorphism and FH in the Saudi population.RESULTSWe confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05–3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13–3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09–2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population.CONCLUSIONIn conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH.LIMITATIONOnly a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

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“… 23 , 24 , 39 – 45 However, there are other variants that are associated with CAD other than the PON1 gene in the global population. 46 – 49 …”

Section: Discussionmentioning

confidence: 99%

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Alharbi

Al-Nbaheen

Alharbi

et al. 2017

Annals of Saudi Medicine

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“…Although research into the functions of IL-8 has proved controversial, most previous studies reporting the contribution of the IL-8 expression to the progression of cardiovascular disorders involved both acute and chronic vascular inflammation [17][18][19][20]. IL-8 is a cytokine that is released in high amounts from neutrophils that participate in all stages of atherosclerosis and the development of CHD [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…IL-8 is a cytokine that is released in high amounts from neutrophils that participate in all stages of atherosclerosis and the development of CHD [17][18][19]. IL-8 is mediated through various mechanisms that contribute to cardiovascular disorders [12][13][14][15][16][17][18][19][20][32][33][34][35][36]. IL-8 from neutrophils was found in both the circulation and the intraplaque of carotid stenosis.…”

Section: Discussionmentioning

confidence: 99%

“…IL-8 is mediated through the downregulation of the tissue inhibitor metalloproteinase-1 to contribute atherogenesis (reviewed in [26,34]). Moreover, the polymorphism of IL-8-251A/T contributes to CHD susceptibility in Chinese populations [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…Prior research on patients and cell culture models [ 8 , 9 ] has shown that IL-8 is involved in the pathogenesis of cardiovascular disorders including CHD [ 10 ], MI [ 11 ], strokes, [ 12 ], and other diseases such as ankylosing spondylitis [ 13 ], emphysema [ 14 ], periodontitis [ 15 ], and systemic lupus erythematosus [ 16 ]. In CVD, IL-8 participates in all stages of atherosclerosis and the development of CHD [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-8 in Hyperlipidemia and Coronary Heart Disease in Thai Patients Taking Statin Cholesterol-Lowering Medication While Undergoing Coronary Artery Bypass Grafting Treatment

et al. 2020

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The role of interleukin-8 (IL-8), a pivotal chemokine in atherogenesis and coronary heart disease (CHD) development, is diverse and remains unclear. This cross-sectional study investigates the association of the IL-8 expression in hyperlipidemia (H) and CHD patients who have been treated with statin cholesterol-lowering drugs while undergoing coronary artery bypass grafting treatment. Fifty-five Thai volunteers including 13 normal (N), 24 H, and 18 CHD patients were enrolled for the investigation. All the CHD patients had been treated continuously with statin cholesterol-lowering medications since the disease was diagnosed and were undergoing coronary bypass grafting approximately one month later. Therefore, the CHD group was representative of a pathogenesis improvement in CHD. The IL8 mRNA expression was determined by real-time quantitative PCR in the peripheral blood mononuclear cells from heparinized blood. The plasma IL-8 levels were assessed by enzyme-linked immunosorbent assay. The result shows that the IL8 mRNA expression in the H group tended to increase; however, in the CHD group, there was a significant decrease (p=0.0111) compared to the N group. The IL8 mRNA expression and the plasma levels in the CHD group were significantly lower than those in the H group (p<0.05). A significant negative correlation between the IL8 mRNA (r = −0.499) or plasma IL-8 (r = −0.3875) expression and CHD progression was observed (p<0.05). In conclusion, the transcriptomic and the phenotypic IL-8 expression decreased significantly in the Thai CHD patients who had continuously received statin-group medications compared to the H and N group participants. Therefore, IL-8 should serve as a feasible marker and could be used to evaluate the therapeutic effects of statins and illustrate the pathology of CHD treatment.

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Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population

2018

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CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (p < 0.001, OR 3.121, 95% CI 1.926-5.056 and p < 0.001, OR 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with p < 0.001, OR 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (p < 0.001, OR 3.693, 95% CI 2.031-6.716; p < 0.001, OR 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (p = 0.010, OR 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (p < 0.001, OR 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (p = 0.039, OR 5.052, 95% CI 1.081-23.602; and p = 0.025, OR 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (p < 0.000, OR 2.964, 95% CI 1.747-5.027; and p < 0.000, OR 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (p < 0.001, OR 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent.

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IL-8 -251A/T polymorphism contributes to coronary artery disease susceptibility in a Chinese population

Cited by 10 publications

References 16 publications

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Interleukin-8 in Hyperlipidemia and Coronary Heart Disease in Thai Patients Taking Statin Cholesterol-Lowering Medication While Undergoing Coronary Artery Bypass Grafting Treatment

Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population

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