Key result
ICAM-1 rs5491 AT genotype linked to ~482% higher odds of ischemic cardiomyopathy versus AA.
Why the study?
A diagnostic model of ischemic cardiomyopathy based on ICAM-1 gene variants had not yet been developed despite known associations between ICAM-1 SNPs and ICM risk.
Case-Control (n=532)
No
Odds Ratio: 5.816 (95% CI 1.661–20.362)
p-value: p=0.006
A novel nomogram incorporating the ICAM-1 rs5491 SNP and clinical variables provides high discriminative accuracy for predicting the risk of ischemic cardiomyopathy.
Should not change practice; hypothesis-generating for ICAM-1 rs5491 in ischemic cardiomyopathy risk.
Objective Previous research has linked single nucleotide polymorphisms (SNPs) in the ICAM-1 gene to an increased risk of developing ischemic cardiomyopathy (ICM); however, a diagnostic model of ICM according to the ICAM-1 variant has not yet been developed. Therefore, this study aimed to explore the correlation between SNPs in ICAM-1 and the presence of ICM, along with developing a diagnostic model for ICM based on the variants of the ICAM-1 gene. Method This study recruited a total of 252 patients with ICM and 280 healthy controls. In addition, all the participants were genotyped for SNPs in the ICAM-1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using the training dataset of 371 people, we constructed a nomogram model based on ICAM-1 gene variants and clinical variables. To optimize the feature choice for the ICM risk model, a least absolute shrinkage and selection operator (LASSO) regression model was adopted. We also employed multivariable logistic regression analysis to build a prediction model by integrating the clinical characteristics chosen in the LASSO regression model. Following the receiver operating characteristic (ROC), a calibration plot and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical usefulness of the predictive model. Result The predictors involved in the prediction nomogram included age, smoking, diabetes, low-density lipoprotein-cholesterol, hemoglobin, N-terminal pro-B-type natriuretic peptide, ejection fraction, and the rs5491 SNP. The nomogram model exhibited good discrimination ability, with the AUC value of ROC of 0.978 (95%CI: 0.967–0.989, P < 0.001) in the training group and 0.983 (95% CI: 0.969–0.998, P < 0.001) in the validation group. The Hosmer–Lemeshow test demonstrated good model calibration with consistency (Ptraining group = 0.937; Pvalidation group = 0.910). The DCA showed that the ICM nomogram was clinically beneficial, with the threshold probabilities ranging from 0.0 to 1.0. Conclusion The AT genotype in rs5491 of the ICAM-1 gene was associated with having a higher frequency of ICM. Individuals carrying the mutant AT genotype showed a 5.816-fold higher frequency of ICM compared with those with the AA genotype. ICM patients with the AT genotype also had a higher rate of cardiogenic death. We, therefore, developed a nomogram model that could offer an individualized prediction of ICM risk factors.
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Naman et al. (2022) conducted a case-control in Ischemic cardiomyopathy (n=532). ICAM-1 gene rs5491 AT genotype vs. ICAM-1 gene rs5491 AA genotype was evaluated on Risk of ischemic cardiomyopathy (OR 5.816, 95% CI 1.661-20.362, p=0.006). Individuals carrying the mutant AT genotype in the ICAM-1 gene rs5491 had a 5.8-fold higher odds of ischemic cardiomyopathy compared to those with the AA genotype (OR 5.816).
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