Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population

Zha, Lingfeng; Dong, Jin‐Tang; Chen, Qianwen; Liao, Yuhua; Zhang, Hongsong; Xie, Tian; Tang, Tingting; Xia, Ni; Zhang, Min; Jiao, Jiao; Zhou, Yingchao; Wu, Jianfei; Yang, Xiaohong; Xu, Chengqi; Wang, Qing K; Tu, Xin; Cheng, Xiang; Nie, Shaofang

doi:10.1016/j.cyto.2021.155761

“…CAD samples and control samples from UnionID were included in our study. The inclusion criteria for CAD samples were [16][17][18] as follows: (1) coronary angiography of the patient confirmed that at least one main vessel (left main artery, anterior descending branch, circumflex branch, or right coronary artery) was more than 70% narrowed; (2) the patient's history suggested that they had undergone percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG); and (3) the patient had a history of myocardial infarction (MI), and the criteria for MI were chest pain for more than half an hour, dynamic ECG changes, and enzymatic changes in levels of creatine kinase isoenzyme (CKMB) and troponin (TNI). Patients with coronary spasm, juvenile hypertension, type 1 diabetes, or congenital heart disease (CHD) were excluded.…”

Section: Study Populationmentioning

confidence: 99%

Genetic Analysis Reveals Different Mechanisms of IL-5 Involved in the Development of CAD in a Chinese Han Population

Zhang

¹

,

He

²

,

Liu

³

et al. 2023

Oxidative Medicine and Cellular Longevity

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Background. Coronary artery disease (CAD) is a complex disease and the leading cause of death worldwide. It is caused by genetic and environmental factors or their interactions. Candidate gene association studies are an important genetic strategy for the study of complex diseases, and multiple variants of inflammatory cytokines have been found to be associated with CAD using this method. Interleukin-5 (IL-5) is an important inflammatory immune response factor that plays a role in a various inflammatory disease. Clinical tests and animal experiments indicated that IL-5 is involved in CAD development, but the exact mechanisms are unclear. This study investigated the genetic relationship between the single nucleotide polymorphisms (SNPs) in IL5 and CAD. Materials and Methods. Based on the Chinese Han population, we collected 1,824 patients with CAD and 1,920 control subjects and performed a two-stage case-control association analysis for three SNPs in IL5 (rs2057687, rs78546665, and rs2069812) using the high resolution melt (HRM) technology. Logistic regression analyses were applied to adjust for traditional risk factors for CAD and to perform haplotype and gene interaction analyses. Multiple linear regression analyses were used to study relationships between the selected SNPs and serum lipid levels. Results. In this study, two-stage case-control association analysis revealed that the allele and genotype frequency distributions of the three IL5 SNPs were not statistically significant between the case and control groups. In addition, none of the IL5 haplotypes were associated with CAD. Further stratified analyses were conducted by sex, age, hypertension, and disease status, respectively, and the results revealed that the rs2057687 and rs2069812 of IL5 were associated with CAD in the male group ( p adj = 0.025 , OR, 0.77 (95% CI, 0.62-0.97); p adj = 0.016 , OR, 0.82 (95% CI, 0.70-0.97), respectively); the rs2057687 and rs78546665 of IL5 were associated with late-onset CAD ( p adj = 0.039 , OR, 0.78 (95% CI, 0.62-0.99); p adj = 0.036 , OR, 1.46 (95% CI, 1.02-1.53), respectively); the rs2069812 of IL5 was associated with CAD in the hypertension group ( p adj = 0.036 , OR, 0.84 (95% CI, 0.71-0.99)); and none of the SNPs in IL5 were associated with different CAD states (anatomical CAD and clinical CAD). In addition, the association between SNPs and the serum lipid levels indicated that rs78546665 was positively correlated with triglyceride levels ( p = 0.012 ). Finally, SNP-SNP interaction analyses revealed that interactions of rs2057687 and rs2069812 were associated with CAD ( p adj = 0.046 , OR, 0.77 (95% CI, 0.13-4.68)). Conclusion. This study suggested that the common variants of IL5 might play a role in CAD by affecting the risk factors for CAD and through SNP-SNP interactions, which provides a new target for specific treatment of CAD patients and a theoretical basis for personalized medicine.

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“…IL12B gene located on chromosome 5q31, a region where we have previously identified multiple CHD susceptibility SNPs. 23,26,28 IL12B was related to lower risk of insulin resistance. However, Morahan et al 31 found rs2853694 was not susceptible to type 1 diabetes.…”

Section: Discussionmentioning

confidence: 91%

“…Of these, 768 CHDs and 768 controls were in the Phase I discovery study, and the remaining samples were used for further extended sample validation of single nucleotide polymorphism (SNP) that showed significant result in Phase I study (Figure 2). All of our samples have been obtained with DNA and relevant clinical information including: age, gender, height, weight, the history of smoking, drinking, hypertension and diabetes, blood lipid and fasting blood glucose, as well as other biochemical detection indicators information 23 . In addition, there are ECG, CT, heart colour ultrasound, coronary angiography and other imaging data of patients with CHD.…”

Section: Methodsmentioning

confidence: 99%

“…All of our samples have been obtained with DNA and relevant clinical information including: age, gender, height, weight, the history of smoking, drinking, hypertension and diabetes, blood lipid and fasting blood glucose, as well as other biochemical detection indicators information. 23 In addition, there are ECG, CT, heart colour ultrasound, coronary angiography and other imaging data of patients with CHD. The inclusion and exclusion criteria for CHD and control were as described in our previous public article 24 , 25 (Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

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Polymorphism of IL‐12/IL‐23 axis is associated with coronary heart disease

Dong,

Chen,

Xie

et al. 2024

J Cellular Molecular Medi

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IL12B encodes the shared p40 subunit (IL‐12p40) of IL‐12 and IL‐23, which have diverse immune functions and are closely related to the occurrence and development of atherosclerosis (AS). However, the exact role of IL12B in coronary heart disease (CHD) was still unknown. A case–control association analysis was performed between five single nucleotide polymorphisms (SNPs) of IL12B (rs1003199, rs3212219, rs2569254, rs2853694 and rs3212227) and CHD in Chinese Han population (1824 patients with CHD vs. 2784 controls). Logistic regression analyses were used to study the relationships between SNPs and CHD, while multiple linear regression analyses were used to test the association between the SNP and the severity of CHD. In addition, the plasma IL12B concentration of CHD patients were detected by ELISA. We detected a significant association between one of the SNPs, rs2853694−G and CHD (padj = 2.075 × 10−5, OR, 0.773 [95% CI, 0.686–0.870]). Stratified analysis showed that rs2853694 was associated with CHD in both male and female populations and was significantly associated with both early‐ and late‐onset CHD. In addition, rs2853694 is also related to the different types of CHD including clinical‐CHD and anatomical‐CHD. Moreover, there are significant differences in serum IL12B concentrations between rs2853694−TT carriers and rs2853694−GT carriers in CHD patients (p = 0.010). A common variant of IL12B was found significantly associated with CHD and its subgroups. As a shared subunit of IL‐12 and IL‐23, IL‐12p40 may play a key role in IL‐12/IL‐23 axis mediated AS, which is expected to be an effective therapeutic target for CHD.

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“…The expression of CCL18 [109], SLAMF7 [110], GPR174 [111], CCR4 [112], POU4F2 [113]. CCR2 [114], IL2RB [115], CCL4 [116], CCL24 [117], FASLG (Fas ligand) [118], CD24 [119], TDGF1 [120], CD28 [121], IL7R [122], CYP11B1 [123], CCL5 [124], CCL3 [125], LTF (lactotransferrin) [126], GPNMB (glycoprotein nmb) [127], CD209 [128], IL2RG [129], CHIT1 [130], TAB2 [131], CD163 [132], ALOX15B [133], NMRK2 [134], HGF (hepatocyte growth factor) [135], TRPM8 [136], DIO3 [137], SIGLEC1 [138], TTR (transthyretin) [139], IL24 [140], F13A1 [141], IL9 [142], VEGFA (vascular endothelial growth factor A) [143], RASAL1 [144], ADM (adrenomedullin) [145], ANGPTL4 [146], CHI3L1 [147], LDB3 [148], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [149], HES6 [150], CMTM5 [151], PLXNB3 [152], KLK8 [153], CDKN1C [154], INSIG1 [155], GREM1 [156], ATF3 [157], HK2 [158], MCAM (melanoma cell adhesion molecule) [159], SEMA4D [160], GLUL (glutamate-ammonia ligase) [161], S1PR5 [162], FN3K [163], MEIS1 [164], ADAMTS4 [165], BIN1 [166], BMP2 [167], LMNA (lamin A/C) [168], ERBB3 [169], DLL1 [170], THBS2 [171], GADD45B [172], MYH6 [173]. PNPLA3 [174], ACTN2 [175], MMP15 [176], SVEP1 [177], CPB2 [178], DYSF (dysferlin) [179], ADAMTSL2 [180], NINJ2 [181], LRP2 [106], PHLDA3 […”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

2

0

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Multiple sclerosis (MS) is the main reason for disability caused by autoimmunity. However, effective biomarkers for MS have not been identified. This study explored the molecular mechanisms and potential therapeutic targets for MS occurrence and progression using bioinformatics and next generation sequencing (NGS) data analysis. NGS data GSE138614, including patients with MS and 25 normal control samples, were obtained from Gene Expression Omnibus (GEO) database Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. Protein–protein interaction (PPI) network and module analyses were performed based on the DEGs. MiRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were built by Cytoscape to predict the underlying microRNAs (miRNAs) and transcription factors (TFs) associated with hub genes. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. A total of 959 DEGs (479 up regulated genes and 480 down regulated genes) were detected. The GO terms and pathways of DEGs involve immune system process, developmental process, immune system and regulation of cholesterol biosynthesis by SREBP (SREBF). The network analysis revealed that hub genes include LCK, PYHIN1, SLAMF1, DOK2, TAB2, CFTR, RHOB, LMNA, EGLN3 and ERBB3 might be involved in the development of MS. The present investigation illustrates a characteristic gene profile in MS, which might contribute to the interpretation of the progression of MS and provide novel biomarkers and therapeutic targets for MS.

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Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population

Cited by 4 publications

References 43 publications

Genetic Analysis Reveals Different Mechanisms of IL-5 Involved in the Development of CAD in a Chinese Han Population

Genetic Analysis Reveals Different Mechanisms of IL-5 Involved in the Development of CAD in a Chinese Han Population

Polymorphism of IL‐12/IL‐23 axis is associated with coronary heart disease

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

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