Dataset Information

Susceptibility of PON1/PON2 Genetic Variations to Ischemic Stroke Risk in a Chinese Han Population.

ABSTRACT:

Background

Paraoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in PON1 and PON2 are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population.

Methods

To investigate the susceptibility of genetic variations in PON1 and PON2 to risk of IS and its subtypes, this case-control study was carried out on a Chinese population comprising 300 IS patients and 300 healthy controls. Genotypes of six genetic variations in PON1 and PON2 were identified with an improved multiplex ligase detection-reaction technique.

Results

PON1 rs662 was associated with increased risk of IS (CT vs. TT - OR_adjusted 1.79, 95% CI 1.08-2.97; p=0.025). Stratified analysis for patients by sex revealed that the significant association of PON1 rs662 with IS risk was maintained in the male cohort (CT vs. TT - OR_adjusted 2.59, 95% CI 1.29-5.21 [p=0.009]; CT/CC vs. TT - OR_adjusted 2.03, 95% CI 1.05-3.93 [p=0.036]), but not in the female cohort. Analysis according to IS subtype revealed that PON1 rs662 genetic variation was an increased risk in the subcohort of patients with large-artery atherosclerosis (CT/CC vs. TT - OR_adjusted 2.31, 95% CI 1.09-4.91; p=0.029), but not in patients with other types of IS.

Conclusion

This study suggested that PON1 rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.

SUBMITTER: Pan Y

PROVIDER: S-EPMC7605958 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Susceptibility of <i>PON1</i>/<i>PON2</i> Genetic Variations to Ischemic Stroke Risk in a Chinese Han Population.

Pan Yuqin Y He Bangshun B Sun Huiling H Xu Tao T Pan Bei B Wang Shukui S Mei Yanping Y

Pharmacogenomics and personalized medicine 20201029

<h4>Background</h4>Paraoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in <i>PON1</i> and <i>PON2</i> are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population.<h4>Methods</h4>To investigate the susceptibility of genetic variations in <i>PON1</i> and <i>PON2</i> to risk of IS and its subtypes, this ca ...[more]

PMID: 33154659

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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.