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Role of IL-9, IL-2RA, and IL-2RB genetic polymorphisms in coronary heart disease

Bedeutung der genetischen Polymorphismen IL-9, IL-2RA und IL-2RB bei koronarer Herzkrankheit

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Abstract

Background

Coronary heart disease (CHD) is one of the leading causes of disability and death worldwide. Inflammatory cytokines play an essential role in the pathogenesis of CHD. This study aimed to detect the potential association between interleukin (IL)-9, IL-2RA, and IL-2RB variants and CHD in a Han Chinese population.

Methods

This case–control study included 499 CHD patients and 496 healthy controls. Seven single-nucleotide polymorphisms (SNPs) were genotyped to investigate the possible association between the polymorphisms and CHD risk. Interactions between SNPs and CHD risk were analyzed via multifactor dimensionality reduction (MDR).

Results

We observed an association between IL‑9 rs55692658 (OR = 1.72, p = 0.003) and increased CHD risk. Age-stratified analysis indicated that regardless of the participantsʼ age, IL‑9 rs55692658 and IL-2RB rs1573673 contributed significantly to CHD susceptibility (p < 0.05, respectively). Results showed an association between IL‑9 rs55692658 and an increased risk for CHD (OR = 2.32, p = 0.003), while IL-2RA rs12722498 was correlated with decreased susceptibility to CHD (OR = 0.54, p = 0.033) in female patients. Furthermore, IL-2RA rs12569923 was related to diabetes risk in CHD patients (OR = 1.50, p = 0.028). The MDR analysis revealed a positive interaction between the SNPs.

Conclusion

The present study demonstrated that IL‑9 rs55692658, IL-2RA rs12569923, IL-2RA rs12722498, and IL-2RB rs3218264 polymorphisms might be related to CHD. The results require validation in larger studies.

Zusammenfassung

Hintergrund

Bei der koronaren Herzkrankheit (KHK) handelt es sich um eine der führenden Ursachen von Behinderung und Tod weltweit. Inflammatorische Zytokine spielen eine essenzielle Rolle in der Pathogenese der KHK. Ziel der vorliegenden Studie war es, den potenziellen Zusammenhang zwischen Varianten von Interleukin (IL)-9, IL-2RA sowie IL-2RB und KHK in einer Population von Han-Chinesen zu untersuchen.

Methoden

Diese Fall-Kontroll-Studie bezog 499-KHK-Patienten und 496 gesunde Kontrollen ein. Eine Genotypisierung erfolgte bei 7 ausgewählten Einzelnukleotidpolymorphismen (SNPs), um eine mögliche Assoziation zwischen den Polymorphismen und dem KHK-Risiko zu ermitteln. Wechselwirkungen zwischen SNPs und KHK-Risiko wurden mittels Multifactor Dimensionality Reduction (MDR) analysiert.

Ergebnisse

Die Autoren stellten einen Zusammenhang zwischen IL-9-rs55692658 (Odds Ratio, OR = 1,72; p = 0,003) und einem erhöhten KHK-Risiko fest. Eine altersstratifizierte Analyse ergab, dass unabhängig vom Alter des Studienteilnehmers IL‑9-rs55692658 und IL-2RB-rs1573673 in signifikanter Weise zur Anfälligkeit für eine KHK beitrugen (p < 0,05 jeweils). Die Ergebnisse zeigten eine Assoziation zwischen IL‑9-rs55692658 und einem erhöhten KHK-Risiko (OR = 2,32; p = 0,003), während IL-2RA-rs12722498 mit einer verminderten Anfälligkeit für eine KHK bei Patientinnen korreliert war (OR = 0,54; p = 0,033). Des Weiteren bestand eine Verknüpfung von IL-2RA-rs12569923 mit dem Diabetesrisiko bei KHK-Patienten (OR = 1,50; p = 0,028). Die MDR-Analyse ergab eine positive Wechselwirkung zwischen den SNPs.

Schlussfolgerung

Die vorliegende Studie zeigte, dass die Polymorphismen IL‑9-rs55692658, IL-2RA-rs12569923, IL-2RA-rs12722498 und IL-2RB-rs3218264 mit KHK in Zusammenhang stehen könnten. Die Ergebnisse erfordern eine Validierung in größeren Studien

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Acknowledgements

We thank all the participants in this study. Furthermore, we are grateful to the clinicians and staff of the Second Affiliated Hospital of Hainan Medical University, as well as the contributors to this study.

Author information

Authors and Affiliations

  1. Department of General Medicine, The Second Affiliated Hospital of Hainan Medical University, 570311, Haikou, China

    Xianghong Chen, Zaozhang Zhang, Yuewu Chen & Chao Wang

  2. Department of Rehabilitative Medicine, The Second Affiliated Hospital of Hainan Medical University, 570311, Haikou, China

    Xingfan Wang

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  1. Xianghong Chen
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  4. Yuewu Chen
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Contributions

Xianghong Chen drafted the manuscript. Xingfan Wang and Zaozhang Zhang performed the DNA extraction and genotyping; Yuewu Chen and Xingfan Wang performed the data analysis; Zaozhang Zhang and Yuewu Chen performed the sample collection and information recording; Xianghong Chen and Chao Wang conceived and supervised the study.

Corresponding author

Correspondence to Chao Wang.

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Conflict of interest

Xianghong Chen, Xingfan Wang, Zaozhang Zhang, Yuewu Chen and Chao Wang declare that they have no competing interests.

This study adhered to the World Medical Association Declaration of Helsinki, and was also approved by the Ethics Committee of the Second Affiliated Hospital of Hainan Medical University. Written informed consent was obtained from each study participant.

Additional information

The authors Xianghong Chen, Xingfan Wang, and Zaozhang Zhang contributed equally to the manuscript.

Caption Electronic Supplementary Material

59_2020_5004_MOESM1_ESM.docx

Supplementary Table 1: Relationships between the SNPs of IL-2RA and IL-2RB and CHD risk; Supplementary Table 2: The SNPs of IL-2RA or IL-2RB associated with CHD risk in the age and gender subgroup tests; Supplementary Table 3: A list of SNPs associated with CHD in the subgroup tests (hypertension vs. non-hypertension and diabetes vs. non-diabetes); Supplementary Table 4: Haplotype frequencies in IL-2RA rs12569923|rs791588 and their association with CHD; Supplementary Figure 1: LD plots of three SNPs in the IL-2RA gene. The number in the diamond indicates the D’ value of pairwise LD between SNPs

59_2020_5004_MOESM2_ESM.tif

Supplementary Figure 1. LD plots of three SNPs in the IL-2RA gene. The number in the diamond indicates the D’ value of pairwise LD between SNPs.

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Chen, X., Wang, X., Zhang, Z. et al. Role of IL-9, IL-2RA, and IL-2RB genetic polymorphisms in coronary heart disease. Herz 46, 558–566 (2021). https://doi.org/10.1007/s00059-020-05004-z

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  • DOI: https://doi.org/10.1007/s00059-020-05004-z

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