Related Experiment Videos
Pai-1 gene variants and COC use are associated with stroke risk: a case-control study in the Han Chinese women
Xiaoping Huang1, Ying Li, Zhizheng Huang
1Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Jiangning District, Nanjing, 211166, Jiangsu, China.
Insights
Genetic variants in the PAI-1 gene influence stroke risk. The 4G allele increases risk, while the 5G allele is protective. Combined oral contraceptive use also affects stroke risk.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
- Pharmacogenomics
Background:
- Plasminogen activator inhibitor type 1 (PAI-1) gene variants may impact stroke pathophysiology.
- Understanding these genetic associations is crucial for stroke risk assessment.
Purpose of the Study:
- To investigate the association between PAI-1 gene polymorphisms and stroke risk.
- To explore the combined effects of PAI-1 variants and combined oral contraceptive (COC) use on stroke risk.
Main Methods:
- A nested case-control study involving 453 female stroke cases and 919 controls.
- Genotyping of PAI-1 SNPs rs1799889, rs7242, and rs2227631.
- Analysis of haplotype associations and gene-environment interactions with COC use.
Main Results:
- The rs1799889 5G allele showed a protective effect against ischemic stroke, while the 4G allele increased risk.
- Combined oral contraceptive users had a 1.31-fold increased stroke risk.
- Specific PAI-1 genotypes and haplotypes demonstrated varied associations with stroke risk, particularly in COC users.
Conclusions:
- PAI-1 gene variants, specifically rs1799889, are associated with ischemic stroke risk in Han Chinese women.
- Combined oral contraceptive use modifies stroke risk in conjunction with PAI-1 gene variants.
- These findings highlight the importance of genetic factors and lifestyle choices in stroke etiology.
Abstract:
Genetic variants of plasminogen activator inhibitor type 1 (PAI-1) gene have been suggested to influence the PAI-1 transcription activity and PAI-1 levels as well as might be involved in the pathophysiology of stroke. The aims of this study are to investigate whether the polymorphisms at the PAI-1 gene are associated with the risk of stroke and to explore the combined effects of PAI-1 variants and combined oral contraceptive (COC) use for stroke risk. We conducted a nested case-control study using 453 first-ever female stroke cases and 919 age- and region-matched controls that were recruited from our prospective surveillance cohort. SNP rs1799889 was genotyped by allele-specific polymerase chain reaction (PCR), and SNPs rs7242 and rs2227631 were detected by the TaqMan SNP genotyping assay. We identified that rs1799889 5G allele conferred a protective effect against ischemic stroke while 4G allele conferred an increased risk of ischemic stroke. But we failed to suggest associations of rs7242 and rs2227631. COC users had a 1.31-fold (OR=1.31, 95% CI=1.01-1.71) increased risk of stroke compared with the non-users. Furthermore, COC users with rs1799889 4G5G/5G5G genotype had a decreased risk of ischemic stroke (OR=0.53, 95% CI=0.34-0.83). Moreover, haplotype G-5G-T was associated with an increased risk of overall stroke (OR=1.28, 95% CI=1.01-1.62). In contrast, haplotype A-4G-G and haplotype G-5G-T were slightly associated with the protection from ischemic stroke (OR=0.61, 95% CI=0.46-0.82; OR=0.61, 95% CI=0.44-0.85, respectively). The study assessed the associations of three PAI-1 SNPs and also suggested combined effects of these PAI-1 gene variants and COC use on stroke risk in the Han Chinese women.