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Association between paraoxonase gene and stroke in the Han Chinese population
Guojun Zhang1, Wenjin Li, Zhiqiang Li
1Laboratory Diagnosis Center, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
Insights
Genetic variants in the paraoxonase (PON1) gene are linked to stroke risk. Specifically, the rs705381 polymorphism in PON1 is associated with reduced risk of total and ischemic stroke in the Han Chinese population.
Area of Science:
- Genetics
- Cardiovascular Disease
- Epidemiology
Background:
- The paraoxonase (PON) gene family (PON1, PON2, PON3) plays a role in preventing oxidative modification of low-density lipoproteins and atherosclerosis.
- Genetic variations in PON genes are investigated for their potential association with cerebrovascular disease risk.
Purpose of the Study:
- To evaluate the association between genetic variants of all three PON genes and the risks of total, ischemic, and hemorrhagic stroke.
- To investigate the role of PON gene polymorphisms in stroke occurrence within the Han Chinese population.
Main Methods:
- A case-control study involving 1016 participants (508 controls, 498 stroke patients).
- Genotyping of 11 single nucleotide polymorphisms (SNPs) across the PON genes.
- Statistical analysis including a dominant model for association and a meta-analysis for specific SNPs (rs662, rs854560) in ischemic stroke.
Main Results:
- The PON1 promoter polymorphism rs705381 (-162) showed a significant association with reduced risk of total stroke (OR=0.57) and ischemic stroke (OR=0.54) under a dominant model.
- No significant association was found between rs705381 and hemorrhagic stroke.
- A nominal association was observed between rs854571 (-824) and total stroke. Meta-analysis indicated a nominal association between rs662 and ischemic stroke.
Conclusions:
- Polymorphisms in the PON1 gene may represent a risk factor for stroke.
- The rs705381 variant in PON1 is associated with a decreased risk of ischemic stroke in the studied population.
Background:
The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population.
Methods:
A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke.
Results:
The presence of rs705381 (-162) in the promoter region of PON1 was significantly associated with total stroke (P(adjusted) = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (P(adjusted) = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (-824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study.
Conclusions:
These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.
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