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Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis

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Abstract

Background

Interleukin-6 (IL-6) is an important mediator of atherosclerotic disease and is also associated with coronary artery disease (CAD). The growing evidences suggest that polymorphisms in the IL-6 promoter region influence the progression of CAD. This study was performed to update the systematic results of association of IL-6 gene polymorphisms with CAD.

Methods

PubMed, Embase, and China Biology Medicine were searched systematically for English and Chinese articles published up to October 31, 2014. Data were extracted using standardized forms. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Subgroup analyses were made on ethnicity.

Results

A total of 42 studies including 15,145 cases and 21,496 controls were combined in this meta-analysis. IL-6 gene −174G/C polymorphism was associated with an increased risk of CAD (for C allele versus G allele: OR = 1.11, 95 % CI 1.02–1.20; for C/C versus G/G: OR = 1.21, 95 % CI 1.03–1.42; for C/C + C/G versus G/G: OR = 1.14, 95 % CI 1.03–1.27). In the subgroup analyses based on ethnicity, a significant association was found between −174 G/C polymorphism and CAD in Caucasians (for C allele versus G allele: OR = 1.12, 95 % CI 1.03–1.22; for C/C versus G/G: OR = 1.21, 95 % CI 1.02–1.42; for C/C + C/G versus G/G: OR = 1.16, 95 % CI 1.05–1.29). In order to reduce heterogeneity, we removed the outlier studies by a Galbraith plot analysis. As a result, the pooled ORs demonstrated no association of −174G/C polymorphism and CAD (C allele versus G allele: OR = 1.02, 95 % CI 0.97–1.06, p = 0.48; C/C versus G/G: OR = 0.1.03, 95 % CI 0.94–1.13, p = 0.48; C/G + C/C versus G/G: OR = 1.03, 95 % CI 0.96–1.09, p = 0.41; C/C versus C/G + G/G: OR = 1.02, 95 % CI 0.94–1.10, p = 0.70, respectively). The polymorphism of −572 G/C was not associated with CAD significantly (for C allele versus G allele: OR = 0.86, 95 % CI 0.74–1.01; C/C versus G/G: OR = 0.99, 95 % CI 0.43–2.27; C/G + C/C versus G/G: OR = 0.96, 95 % CI 0.80–1.15, respectively). In addition, subgroup analyses showed an association between −572 G/C polymorphism and CAD risk among Chinese (C allele versus G allele: OR = 0.64, 95 % CI 0.48–0.85; C/C versus G/G: OR = 0.38, 95 % CI 0.18–0.81; C/G + C/C versus G/G: OR = 0.47, 95 % CI 0.22–1.00; C/C versus C/G + G/G: OR = 0.58, 95 % CI 0.42–0.81).

Conclusion

The C allele of −174G/C polymorphism may associate with increased sensibility to CAD among Caucasians in overall analysis. Nevertheless, the effect is interfered by heterogeneity across the included studies. The C allele of −572G/C polymorphism may decrease the risk of CAD in Chinese.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grants: NSFC, No. 81202170), Taian Science and Technology Foundation (No. 20103012).

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The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Taishan Medical University, No. 2 YingSheng East Road, Taian, 271000, People’s Republic of China

      Haifeng Hou, Chenglin Wang, Linlin Zhao, Aishe Dun & Zheng Sun

    2. Taishan Hospital, Taian, Shandong, People’s Republic of China

      Fengjing Sun

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    1. Haifeng Hou
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    Correspondence to Haifeng Hou or Zheng Sun.

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    Responsible Editor: Yoshiya Tanaka.

    H. Hou and C. Wang contributed equally to this work.

    Electronic supplementary material

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    11_2015_850_MOESM1_ESM.tif

    Forest plot of the association between allele model of −174 G/C polymorphism and CAD in South Asian. Each study is shown by an OR and the 95 % CI. The random effects pooled ORs are shown. (TIFF 97 kb)

    11_2015_850_MOESM2_ESM.tif

    Forest plot of the association between additive model of −174 G/C polymorphism and CAD in South Asian. Each study is shown by an OR and the 95 % CI. The random effects pooled ORs are shown. (TIFF 98 kb)

    11_2015_850_MOESM3_ESM.tif

    Forest plot of the association between dominant model of −174 G/C polymorphism and CAD in South Asian. Each study is shown by an OR and the 95 % CI. The random effects pooled ORs are shown. (TIFF 116 kb)

    11_2015_850_MOESM4_ESM.tif

    Forest plot of the association between recessive model of −174 G/C polymorphism and CAD in South Asian. Each study is shown by an OR and the 95 % CI. The random effects pooled ORs are shown. (TIFF 118 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in allele model. (TIFF 167 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in additive model. (TIFF 165 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in dominant model. (TIFF 145 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in recessive model. (TIFF 143 kb)

    Funnel plots for IL-6 gene-572 G/C polymorphism and CAD risk in allele model. (TIFF 280 kb)

    Funnel plots for IL-6 gene-572 G/C polymorphism and CAD risk in additive model. (TIFF 278 kb)

    Funnel plots for IL-6 gene-572 G/C polymorphism and CAD risk in dominant model. (TIFF 279 kb)

    Funnel plots for IL-6 gene-572 G/C polymorphism and CAD risk in recessive model. (TIFF 273 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in allele model among South Asian. (TIFF 37 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in additive model among South Asian. (TIFF 37 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in dominant model among South Asian. (TIFF 38 kb)

    Funnel plots for IL-6 gene−174G/C polymorphism and CAD risk in recessive model among South Asian. (TIFF 37 kb)

    11_2015_850_MOESM17_ESM.doc

    Characteristics of case/control definitions in the studies of IL-6 gene −174G > C polymorphism included in the meta-analyses. Characteristics of case/control definitions in the studies of IL-6 gene -572C > G polymorphism included in the meta-analyses. Studies of IL-6 gene -174G > C polymorphism included in the meta-analyses.Studies of IL-6 gene -572C > G polymorphism included in the meta-analyses. Results of meta-regression analyses for -174G > C polymorphism. (DOC 259 kb)

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    Hou, H., Wang, C., Sun, F. et al. Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis. Inflamm. Res. 64, 707–720 (2015). https://doi.org/10.1007/s00011-015-0850-9

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