Limits...
A promoter polymorphism (rs17222919, -1316T/G) of ALOX5AP gene is associated with decreased risk of ischemic stroke in two independent Chinese populations.

Fan Y, Chen H, Li A, Shi Y, Zhang Y, Feng Q, Sun Y, Zheng H, He Y - PLoS ONE (2015)

Bottom Line: After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively).Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031).Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Medical Genetics, Basic Medical College of Zhengzhou University, Zhengzhou, China.

ABSTRACT
No coding sequence variants of the gene encoding 5-lipoxygenase-activating protein (ALOX5AP) leading to amino acid substitutions have been identified. Therefore, variants in the ALOX5AP promoter region have received attention recently. The purpose of this study was to explore whether the promoter polymorphism rs17222919 is involved in the etiology of ischemic stroke (IS) in the Chinese Han population. We investigated the rs17222919 polymorphism by TaqMan genotyping in two independent Chinese Han samples: the first comprised 910 IS patients and 925 healthy inhabitants from the northern Henan Province, while the second included 1003 IS patients and 889 healthy controls from the southern Henan Province. Functional characterization of rs17222919 was performed by an in vitro luciferase assay. After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively). This was also observed in the large-artery atherosclerosis (LAA) and stroke of other undetermined etiology (SUE) subtypes (P = 0.019, OR = 0.815, 95% CI = 0.687-0.967; P = 0.021, OR = 0.815, 95% CI = 0.685-0.970, respectively). Additionally, the TG genotype and G allele frequencies were significantly lower in the IS compared with the control group in two female cohorts (P<0.05). Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031). Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

No MeSH data available.


Related in: MedlinePlus

Effects of the promoter Polymorphism (rs17222919, −1316T/G) of ALOX5AP gene on transcriptional activity.The transcription activity was measured using an in vitro luciferase assay and the results were shown as the means ± SE values. Data were expressed as the fold-increase in luciferase activity relative to pGL3- promoter. A one-way ANOVA was used to assess statistical significance.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4376390&req=5

pone.0122393.g001: Effects of the promoter Polymorphism (rs17222919, −1316T/G) of ALOX5AP gene on transcriptional activity.The transcription activity was measured using an in vitro luciferase assay and the results were shown as the means ± SE values. Data were expressed as the fold-increase in luciferase activity relative to pGL3- promoter. A one-way ANOVA was used to assess statistical significance.

Mentions: We next investigated whether the polymorphism at position −1316 affected the transcriptional activity of the ALOX5AP promoter in HEK293 cells. The experiments showed that significantly lower levels of luciferase were produced by the G allele construct compared with the T allele construct (P = 0.031, Fig 1), although these levels were higher than the pGL3-promoter reference vector (P = 0.000). This suggested that the G allele has a lower transcription activity than the T allele.


A promoter polymorphism (rs17222919, -1316T/G) of ALOX5AP gene is associated with decreased risk of ischemic stroke in two independent Chinese populations.

Fan Y, Chen H, Li A, Shi Y, Zhang Y, Feng Q, Sun Y, Zheng H, He Y - PLoS ONE (2015)

Effects of the promoter Polymorphism (rs17222919, −1316T/G) of ALOX5AP gene on transcriptional activity.The transcription activity was measured using an in vitro luciferase assay and the results were shown as the means ± SE values. Data were expressed as the fold-increase in luciferase activity relative to pGL3- promoter. A one-way ANOVA was used to assess statistical significance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376390&req=5

pone.0122393.g001: Effects of the promoter Polymorphism (rs17222919, −1316T/G) of ALOX5AP gene on transcriptional activity.The transcription activity was measured using an in vitro luciferase assay and the results were shown as the means ± SE values. Data were expressed as the fold-increase in luciferase activity relative to pGL3- promoter. A one-way ANOVA was used to assess statistical significance.
Mentions: We next investigated whether the polymorphism at position −1316 affected the transcriptional activity of the ALOX5AP promoter in HEK293 cells. The experiments showed that significantly lower levels of luciferase were produced by the G allele construct compared with the T allele construct (P = 0.031, Fig 1), although these levels were higher than the pGL3-promoter reference vector (P = 0.000). This suggested that the G allele has a lower transcription activity than the T allele.

Bottom Line: After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively).Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031).Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Medical Genetics, Basic Medical College of Zhengzhou University, Zhengzhou, China.

ABSTRACT
No coding sequence variants of the gene encoding 5-lipoxygenase-activating protein (ALOX5AP) leading to amino acid substitutions have been identified. Therefore, variants in the ALOX5AP promoter region have received attention recently. The purpose of this study was to explore whether the promoter polymorphism rs17222919 is involved in the etiology of ischemic stroke (IS) in the Chinese Han population. We investigated the rs17222919 polymorphism by TaqMan genotyping in two independent Chinese Han samples: the first comprised 910 IS patients and 925 healthy inhabitants from the northern Henan Province, while the second included 1003 IS patients and 889 healthy controls from the southern Henan Province. Functional characterization of rs17222919 was performed by an in vitro luciferase assay. After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively). This was also observed in the large-artery atherosclerosis (LAA) and stroke of other undetermined etiology (SUE) subtypes (P = 0.019, OR = 0.815, 95% CI = 0.687-0.967; P = 0.021, OR = 0.815, 95% CI = 0.685-0.970, respectively). Additionally, the TG genotype and G allele frequencies were significantly lower in the IS compared with the control group in two female cohorts (P<0.05). Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031). Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

No MeSH data available.


Related in: MedlinePlus