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Genetic polymorphisms in pri-let-7a-2 are associated with ischemic stroke risk in a Chinese Han population from Liaoning, China: a case-control study.

ABSTRACT: Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms. Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke. Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs. In this case-control study, we analyzed the distribution of pri-let-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors. Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University. We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke. Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample. We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension. Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China (approval No. 2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559) on December 27, 2017.

SUBMITTER: Wang YY

PROVIDER: S-EPMC8284288 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesStroke is the most common cause of disability and the second cause of death worldwide. Therefore, there is a need to identify patients at risk of developing stroke. This case-control study aimed to create and verify a gender-specific genetic signature-based nomogram to facilitate the prediction of ischemic stroke (IS) risk using only easily available clinical variables.Materials and methodsA total of 1,803 IS patients and 1,456 healthy controls from the Liaoning province in China (Han population) were included which randomly divided into training cohort (70%) and validation cohort (30%) using the sample function in R software. The distribution of the pri-let-7f-2 rs17276588 variant genotype was analyzed. Following genotyping analysis, statistical analysis was used to identify relevant features. The features identified from the multivariate logistic regression, the least absolute shrinkage and selection operator (LASSO) regression, and univariate regression were used to create a multivariate prediction nomogram model. A calibration curve was used to determine the discrimination accuracy of the model in the training and validation cohorts. External validity was also performed.ResultsThe genotyping analysis identified the A allele as a potential risk factor for IS in both men and women. The nomogram identified the rs17276588 variant genotype and several clinical parameters, including age, diabetes mellitus, body mass index (BMI), hypertension, history of alcohol use, history of smoking, and hyperlipidemia as risk factors for developing IS. The calibration curves for the male and female models showed good consistency and applicability.ConclusionThe pri-let-7f-2 rs17276588 variant genotype is highly linked to the incidence of IS in the northern Chinese Han population. The nomogram we devised, which combines genetic fingerprints and clinical data, has a lot of promise for predicting the risk of IS within the Chinese Han population.

Project description:Numerous genetic polymorphisms and clinical laboratory parameters are associated with ischemic stroke (IS). However, the results of such studies have frequently been inconsistent. The aim of the present study was to evaluate associations between clinical laboratory parameters with genetic polymorphisms that influence the risk of IS in a Chinese Han population. Clinical laboratory parameters were measured by an automatic biochemical analyzer. Genotype and allele frequencies of the polymorphisms angiotensin-converting enzyme (ACE) D/I, methylene tetrahydrofolate reductase (MTHFR) C677T and β-fibrinogen (β-Fg) A/G, 455/148T/C were characterized by restriction fragment length polymorphism-PCR. Furthermore, the gene polymorphisms plasminogen activator inhibitor (PAI)-1-4G/5G and apolipoprotein E (ApoE) ε2,3,4 were characterized by allele-specific PCR. The associations of genotype and allele frequencies of the six risk genes in different groups with clinical laboratory parameters were analyzed by chi-square tests. The distribution maps of the polymorphisms of the six genes and clinical laboratory parameters were compared between a control group of 336 healthy individuals and 762 patients with IS. Certain laboratory parameters were associated with ACE I/D, β-Fg-455 A/G and PAI-1 4G/5G. The D allele of ACE I/D was associated with high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). Furthermore, high levels of fasting blood glucose, triglyceride and LDL-C were risk factors for IS. There were significant differences in the genotype frequencies of ACE I/D, β-Fg-455 A/G and β-Fg-148 T/C between the IS and the control group. In conclusion, clinical laboratory parameters were associated with the risk of polymorphisms of IS-related genes. The present results support the determination of a range of control values of clinical laboratory parameters for common genotypes in patients with diabetes and hyperlipidemia as a strategy for the early prevention of IS.

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Genetic polymorphisms in pri-let-7a-2 are associated with ischemic stroke risk in a Chinese Han population from Liaoning, China: a case-control study.

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