Systematic review and meta-analysis of association of polymorphisms in inflammatory cytokine genes with coronary artery disease

Tabaei, Samira; Motallebnezhad, Morteza; Tabaee, Seyedeh Samaneh

doi:10.1007/s00011-020-01385-3

Cited by 8 publications

(11 citation statements)

References 79 publications

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“…There have been at least 12 published meta-analyses investigating the association of common IL6 SNPs with CAD, myocardial infarction (MI; or surrogates), and related clinical presentations. [5][6][7][9][10][11][12][13][14][15][16][17] However, flawed ethnic stratifications in these meta-analyses yielded inconsistent results [5][6][7][9][10][11][12][13][14][15][16][17]. Against this background, our objectives in this systematic review and metaanalysis were to: (i) ascertain the overall association of IL6 -174 G/C polymorphism with CAD, as well as separately amongst different ancestral populations, (ii) investigate the association of this polymorphic form with circulating IL-6 levels.…”

Section: Introductionmentioning

confidence: 99%

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis

Rai¹,

Colleran²,

Cassese

et al. 2021

Inflamm. Res.

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Introduction Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 -174 G/C, rs1800795) have been shown to be independently associated with coronary artery disease (CAD) by several investigators. Despite more than 12 published meta-analyses on this subject, association of -174 G/C with CAD, especially amongst distinct ancestral population groups remain unclear. We, therefore, conducted a systematic review and an updated meta-analysis to comprehensively ascertain the association of IL6 -174 G/C with CAD and circulating IL-6 levels. Materials and methods Relevant case–control/cohort studies investigating association of -174 G/C with CAD and circulating IL-6 levels were identified following a comprehensive online search. Association status for CAD was determined for the pooled sample, as well as separately for major ancestral subgroups. Association status for circulating IL-6 levels was assessed for the pooled sample, as well as separately for CAD cases and CAD free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled using random/fixed-effects model. Results Quantitative synthesis for the CAD endpoint was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases/32,053 controls). Pooled association of -174 G/C with CAD was found to be statistically significant through dominant (OR 1.15; 95% CI 1.05–1.25, p = 0.002) as well as allelic genetic model comparisons (OR 1.13, 95% CI 1.06–1.21, p = 0.0003). This effect was largely driven by Asian and Asian Indian ancestral subgroups, which also showed significant association with CAD in both genetic model comparisons (OR range 1.29–1.53, p value range ≤ 0.02). Other ancestral subgroups failed to show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the ‘C’ allele carriers in the pooled sample (Standard mean difference, SMD 0.11, 95% CI 0.01–0.22 pg/ml, p = 0.009) as well as in the CAD free control subgroup (SMD 0.10, 95% CI 0.02–0.17 pg/ml, p = 0.009), though not in the CAD case subgroup (SMD 0.17, 95% CI = − 0.02 to 0.37, p = 0.12). Conclusions The present systematic review and meta-analysis demonstrate an overall association between IL6 -174 G/C polymorphism and CAD, which seems to be mainly driven by Asian and Asian Indian ancestral subgroups. Upregulation of plasma IL-6 levels in the ‘C’ allele carriers seems to be at least partly responsible for this observed association. This warrants further investigations with large, structured case–control studies especially amongst Asian and Asian Indian ancestral groups.

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Section: Introductionmentioning

confidence: 99%

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis

Rai¹,

Colleran²,

Cassese

et al. 2021

Inflamm. Res.

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“…So far, more than 60 genetic variants have been confirmed to be associated with increased susceptibility to CAD using genome‐wide association studies (GWAS) 4 . Previous studies have shown that genes related to CAD mainly include genes related to vascular structure and function, lipid metabolism, and inflammatory cytokines 5‐7 …”

Section: Introductionmentioning

confidence: 99%

“…4 Previous studies have shown that genes related to CAD mainly include genes related to vascular structure and function, lipid metabolism, and inflammatory cytokines. [5][6][7] Apolipoprotein E (ApoE) is one of the apolipoproteins of chylomicron, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low-density lipoproteincholesterol (VLDL-C), which plays an important role in regulating lipoprotein metabolism. ApoE is a multifunctional protein that plays an important role in lipid metabolism by binding to LDL receptors and mediating the removal of chylomicron and VLDL from serum.…”

Section: Introductionmentioning

confidence: 99%

APOE gene ɛ4 allele (388C‐526C) effects on serum lipids and risk of coronary artery disease in southern Chinese Hakka population

Liu

et al. 2021

Clinical Laboratory Analysis

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Objective To analyze the relationship of Apolipoprotein E (APOE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene polymorphisms with coronary artery disease (CAD). Methods 1,129 CAD patients and 1,014 non‐CAD controls were included in the study, and relevant information and medical records were collected. The single‐nucleotide polymorphisms (SNPs) were analyzed, including rs429358, rs7412 in APOE gene and rs2306283, rs4149056 in SLCO1B1 gene. Results The CAD patients’ average age was 66.3 ± 10.7 years, while 65.5 ± 12.0 years in controls. The frequencies of APOE allele ɛ3, ɛ4, and ɛ2 were 83.01%, 10.08%, and 6.91% respectively. There were statistically significant differences in genotype ɛ3/ɛ4 (χ2 = 8.077, p = 0.005) in CAD patients compared with the controls. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. Moreover, ε4 carriers had significantly lower HDL‐C, Apo‐A1 levels than ε3 carriers among CAD patients, while ε2 carriers showed lower LDL‐C, Apo‐B level, and higher Apo‐A1/Apo‐B level than ε3 and ε4 carriers. In controls, ε2 carriers showed lower LDL‐C and Apo‐B level, higher Apo‐A1, and Apo‐A1/Apo‐B level than ε4 carriers. Logistic regression analysis showed that high LDL‐C and Apo‐B level, low HDL‐C level, smoking, and the ε4 allele were risks for the presence of CAD. Conclusions APOE ε4 allele may be associated with susceptibility to CAD in southern Chinese Hakka population. It indicated that the APOE SNPs rs429358 and rs7412 are associated with CAD, but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene.

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“…Этот риск существенно возрастает и у носителей гаплотипов GG и AG полиморфизмов TNF-α -308 (G/A) и TNF-β +252 (A/G). Не удалось установить связь ИБС с полиморфизмом TNF-α -238G/A (rs361525) при метаанализе с участием 5062 пациентов [8].…”

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“…По результатам метаанализа полиморфизма -572G/С гена IL-6 у 4545 пациентов и 7720 контрольных лиц обнаружено достоверное увеличение риска возникновения ИБС в случае доминантной модели (CC + GC vs. GG), аллельной модели (G vs. C) и гетерозиготного сравнения (GC vs.CC) [9]. Связь риска ИБС с полиморфизмом -572G/С гена IL-6 подтвердила и другая исследовательская группа в недавнем метаанализе, включавшем 13 801 пациента [8]. Выявленные риски не соответствуют либо представлению о более низкой экспрессии IL-6 у носителей аллели G полиморфизма -572G/С, либо данным о росте риска ИБС с увеличением содержания в крови IL-6.…”

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Singlenucleotide polymorphisms in cytokine genes and their role in the pathogenesis of cardiac , vascular and pulmonary diseases

Sergey¹,

Peregud²,

Nn³

et al. 2021

Medical news of the North Caucasus

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университет им. И. М. Сеченова, (Сеченовский Университет), Российская Федерация 2 Национальный медицинский исследовательский центр психиатрии и наркологии им. В. п. Сербского, Москва, Российская Федерация 3 Российский университет дружбы народов, Москва, Российская Федерация single nucleoTide polYmorphisms in cYToKine genes and Their role in The paThogenesis of cardiac, Vascular and pulmonarY diseases pirozhkov s. V. 1 , peregud d. i. 2 , Terebilina n. n. 2 , litvitskiy p. f. 1 , Kabaeva e. n. 3 1 i. m. sechenov first moscow state medical university (sechenov university), russian federation 2 V. p. serbsky national medical research center for psychiatry and addiction, moscow, russian federation 3 peoples' frendship university, moscow, russian federationПроведен анализ современных данных о влиянии полиморфизмов генов цитокинов на возникновение, течение, проявления и исходы наиболее распространенных сердечных, сосудистых и легочных заболеваний человека, в патогенезе которых воспаление играет существенную роль. Спектр рассматриваемых цитокинов включает классы, потенцирующие воспалительный процесс (провоспалительные цитокины), такие как TNF-α, IL-1, IL-6, IL-12, IL-13, IL-17 и IL-33, и ингибирующие его (антивоспалительные), которыми считают IL-10, IL-4, TGF-β. Обсуждается роль полиморфизмов цитокинов в развитии дилятационной кардиомиопатии, ишемической болезни сердца, сердечной недостаточности, инсульта, бронхиальной астмы, хронической обструктивной болезни легких. Полученные данные свидетельствуют, что содержание и выраженность эффекта на патологический процесс полиморфизмов генов цитокинов зависят от локализации полиморфного участка, его влияния на экспрессию гена, от комбинации аллелей полиморфизмов и этнической принадлежности пациентов.Ключевые слова: цитокины, однонуклеотидный полиморфизм, дилятационная кардиомиопатия, ишемическая болезнь сердца, инсульт, ревматоидный артрит, бронхиальная астма, хроническая обструктивная болезнь легкихThe purpose of the literature review is to analyze the current data on the influence of cytokine gene polymorphisms on the occurrence, course, manifestations and outcomes of the most common cardiac, vascular and pulmonary diseases, in the pathogenesis of which inflammation plays a significant role. The range of cytokines under consideration includes classes that potentiate the inflammatory process (pro-inflammatory cytokines), which include TNF-α, IL-1, IL-6, IL-12, IL-13, IL-17 and IL-33, and its inhibitors (anti-inflammatory), such as IL-10, IL-4, TGF-β. The role of cytokine polymorphisms

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Systematic review and meta-analysis of association of polymorphisms in inflammatory cytokine genes with coronary artery disease

Cited by 8 publications

References 79 publications

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis

APOE gene ɛ4 allele (388C‐526C) effects on serum lipids and risk of coronary artery disease in southern Chinese Hakka population

Singlenucleotide polymorphisms in cytokine genes and their role in the pathogenesis of cardiac , vascular and pulmonary diseases

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