Association of interleukin-6 circulating levels with coronary artery disease: A meta-analysis implementing mendelian randomization approach

AbstractThe relationships between the rs266729, rs1501299, and rs2241766 polymorphisms in adiponectin gene (ADIPOQ) and circulating levels of adiponectin and lipids remain to be clarified. Databases including PubMed and Embase were searched for eligible studies. The random-effects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in circulating levels of adiponectin and lipids between the subjects with different genotypes. A total of 12 810, 17 319, and 21 361 subjects were identified in the analyses for the rs266729, rs1501299, and rs2241766 polymorphisms, respectively. G allele carriers of the rs266729 polymorphism had lower levels of adiponectin (SMD=–0.28, 95% CI=–0.43 to–0.12) and high-density lipoprotein cholesterol (HDL-C) (SMD=–0.10, 95% CI=–0.17 to–0.02) than CC homozygotes; T allele carriers of the rs1501299 polymorphism had higher levels of adiponectin (SMD=0.21, 95% CI=0.05 to 0.36) and HDL-C (SMD=0.09, 95% CI=0.04 to 0.15) and lower levels of triglycerides (SMD=–0.06, 95% CI=–0.12 to–0.01) than GG homozygotes; G allele carriers of the rs2241766 polymorphism had lower levels of adiponectin (SMD=–0.18, 95% CI=–0.31 to–0.05) and HDL-C (SMD=–0.12, 95% CI=–0.20 to–0.04) than TT homozygotes. This meta-analysis suggests that the rs266729, rs1501299, and rs2241766 polymorphisms of ADIPOQ are significantly associated with circulating levels of adiponectin and lipids, which may partly explain the associations between these polymorphisms and coronary artery disease.

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Is interleukin-6 circulating levels associated with coronary artery disease?

International Journal of Cardiology ◽

10.1016/j.ijcard.2012.03.015 ◽

2012 ◽

Vol 157 (2) ◽

pp. 270 ◽

Cited By ~ 1

Author(s):

Chibo Liu

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

Artery Disease ◽

Circulating Levels

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Negative Effects of Age at Menarche on Risk of Cardiometabolic Diseases in Adulthood: A Mendelian Randomization Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz071 ◽

2019 ◽

Vol 105 (2) ◽

pp. 515-522 ◽

Cited By ~ 3

Author(s):

Min Cao ◽

Bin Cui

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Mendelian Randomization ◽

Causal Effect ◽

Meta Analysis ◽

Age At Menarche ◽

Model Assessment ◽

Cardiometabolic Diseases ◽

Genome Wide ◽

Artery Disease

Abstract Context Observational studies have demonstrated that early menarche is associated with cardiometabolic diseases, but confounding factors make it difficult to infer causality. Objective We used Mendelian randomization (MR) to examine whether age at menarche (AAM) is causally associated with type 2 diabetes (T2D), coronary artery disease (CAD) and cardiometabolic traits. Design and Methods A 2-sample MR analysis was conducted using genome-wide association study (GWAS) summary statistics from the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium (n = 159 208) for T2D and the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) consortium (n = 184 305) for CAD. We used 122 instrumental variables (IVs) extracted from a published GWAS meta-analysis incorporating 182 416 women to determine the causal effect of AAM on cardiometabolic diseases, treating childhood and adult body mass index (BMI) as the confounders. Sensitivity analyses were also performed to detect the pleiotropy of the IVs. Results Employing the MR approach, we found that later AAM was associated with decreased risk of CAD (OR, 0.92 [95% CI, 0.88-0.96]; P = 2.06 × 10–4) in adults, as well as lower blood levels of log fasting insulin, log homeostatic model assessment of insulin resistance (HOMA-IR), log HOMA of β-cell function (HOMA-B), triglycerides, and diastolic blood pressure, but higher blood level of high-density lipoprotein. However, the associations were substantially attenuated after excluding BMI-related variants. MR analyses provide little evidence on the causal effect between AAM and T2D. Conclusions Our findings showed that AAM did not appear to have a causal effect on the risk of cardiometabolic diseases in adult life, as their associations observed in epidemiological studies might be largely mediated through excessive adiposity. We propose adiposity might be a primary target in future intervention strategy.

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The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis

Genes and Environment ◽

10.1186/s41021-021-00172-8 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Nader Salari ◽

Kamran Mansouri ◽

Amin Hosseinian-Far ◽

Hooman Ghasemi ◽

Masoud Mohammadi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

Odds Ratio ◽

Meta Analysis ◽

Serum Levels ◽

Protective Effects ◽

Increased Risk ◽

Artery Disease ◽

The Relationship

Abstract Background Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease. Methods This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software. Results The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85. Conclusion This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

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Desaturase Activity and the Risk of Type 2 Diabetes and Coronary Artery Disease: A Mendelian Randomization Study

Nutrients ◽

10.3390/nu12082261 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2261 ◽

Cited By ~ 1

Author(s):

Susanne Jäger ◽

Rafael Cuadrat ◽

Per Hoffmann ◽

Clemens Wittenbecher ◽

Matthias B. Schulze

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Fatty Acids ◽

Coronary Artery ◽

Cardiometabolic Risk ◽

Mendelian Randomization ◽

Meta Analysis ◽

Genome Wide ◽

Artery Disease

Estimated Δ5-desaturase (D5D) and Δ6-desaturase (D6D) are key enzymes in metabolism of polyunsaturated fatty acids (PUFA) and have been associated with cardiometabolic risk; however, causality needs to be clarified. We applied two-sample Mendelian randomization (MR) approach using a representative sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study and public data from DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) genome-wide association studies (GWAS). Furthermore, we addressed confounding by linkage disequilibrium (LD) as all instruments from FADS1 (encoding D5D) are in LD with FADS2 (encoding D6D) variants. Our univariable MRs revealed risk-increasing total effects of both, D6D and D5D on type 2 diabetes (T2DM) risk; and risk-increasing total effect of D6D on risk of coronary artery disease (CAD). The multivariable MR approach could not unambiguously allocate a direct causal effect to either of the individual desaturases. Our results suggest that D6D is causally linked to cardiometabolic risk, which is likely due to downstream production of fatty acids and products resulting from high D6D activity. For D5D, we found indication for causal effects on T2DM and CAD, which could, however, still be confounded by LD.

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