Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis.
In: Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jg. 70 (2021-12-01), Heft 10-12, S. 1075-1087
Online
academicJournal
Zugriff:
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.
(© 2021. The Author(s).)
Titel: |
Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis.
|
---|---|
Autor/in / Beteiligte Person: | Rai, H ; Colleran, R ; Cassese, S ; Joner, M ; Kastrati, A ; Byrne, RA |
Link: | |
Zeitschrift: | Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jg. 70 (2021-12-01), Heft 10-12, S. 1075-1087 |
Veröffentlichung: | Basel, Switzerland : Birkhäuser, c1995-, 2021 |
Medientyp: | academicJournal |
ISSN: | 1420-908X (electronic) |
DOI: | 10.1007/s00011-021-01505-7 |
Schlagwort: |
|
Sonstiges: |
|