Tags

Type your tag names separated by a space and hit enter

Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke.
Cerebrovasc Dis. 2011; 32(3):261-8.CD

Abstract

BACKGROUND

Despite accumulating evidence supporting the association between variants of the ALOX5AP gene and atherosclerotic vascular events, the precise mechanism is still unclear. No variants in the coding sequence that lead to amino acid substitution have been found. We investigated genetic variants in the promoter region of the ALOX5AP gene and the association with ischemic stroke in a north Chinese Han population.

METHODS

505 cases of ischemic stroke and 500 age- and gender-matched controls of the north Chinese Han population were enrolled. Genetic variants in the promoter region of the ALOX5AP gene were identified by polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were randomly selected and compared for serum leukotriene B(4) (LTB(4)) concentration. The effect on ischemic stroke was evaluated by logistic regression.

RESULTS

Three genetic variants were identified, including a mutation (-519 G > A), an insertion and deletion polymorphisms (-581_582 Ins A) and a single nuclear polymorphisms (-946 A > G). Association study showed that the II genotype of -581_582 Ins A was significantly associated with ischemic stroke of a large artery atherosclerosis (OR = 3.50, 95% CI = 1.93-6.36, p = 0.0002) and undetermined etiology (OR = 3.66, 95% CI = 1.92-6.94, p = 0.0006). No significant association was found between the -519 GA genotype (OR = 0.35, 95% CI = 0.02-5.88, p = 0.46), -946 AG genotype (OR = 1.35, 95% CI = 0.85-2.16, p = 0.21) and ischemic stroke. There was no significant difference in serum LTB(4) concentration between cases (n = 40) and controls (n = 40) (log serum LTB(4) of cases vs. controls: 2.67 ± 0.14 vs. 2.73 ± 0.18 pg/ml, p = 0.10). However, the serum LTB(4) concentration was significantly higher in participants with the II genotype of -581_582 Ins A (n = 12) than that of participants with the DD genotype (n = 68) (log serum LTB(4) of participants with II genotype vs. DD genotype: 2.82 ± 0.18 vs. 2.68 ± 0.15 pg/ml, p = 0.01).

CONCLUSION

The -581_582 Ins A polymorphism might be a novel genetic risk factor for ischemic stroke in a north Chinese Han population. Further studies on molecular mechanism are warranted.

Authors+Show Affiliations

Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China. JRJChina@sina.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21893978

Citation

Ji, Ruijun, et al. "Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke." Cerebrovascular Diseases (Basel, Switzerland), vol. 32, no. 3, 2011, pp. 261-8.
Ji R, Jia J, Ma X, et al. Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke. Cerebrovasc Dis. 2011;32(3):261-8.
Ji, R., Jia, J., Ma, X., Wu, J., Zhang, Y., & Xu, L. (2011). Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke. Cerebrovascular Diseases (Basel, Switzerland), 32(3), 261-8. https://doi.org/10.1159/000330341
Ji R, et al. Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke. Cerebrovasc Dis. 2011;32(3):261-8. PubMed PMID: 21893978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke. AU - Ji,Ruijun, AU - Jia,Jianping, AU - Ma,Xin, AU - Wu,Jian, AU - Zhang,Yanli, AU - Xu,Liqing, Y1 - 2011/08/31/ PY - 2011/01/24/received PY - 2011/05/20/accepted PY - 2011/9/7/entrez PY - 2011/9/7/pubmed PY - 2012/1/27/medline SP - 261 EP - 8 JF - Cerebrovascular diseases (Basel, Switzerland) JO - Cerebrovasc Dis VL - 32 IS - 3 N2 - BACKGROUND: Despite accumulating evidence supporting the association between variants of the ALOX5AP gene and atherosclerotic vascular events, the precise mechanism is still unclear. No variants in the coding sequence that lead to amino acid substitution have been found. We investigated genetic variants in the promoter region of the ALOX5AP gene and the association with ischemic stroke in a north Chinese Han population. METHODS: 505 cases of ischemic stroke and 500 age- and gender-matched controls of the north Chinese Han population were enrolled. Genetic variants in the promoter region of the ALOX5AP gene were identified by polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were randomly selected and compared for serum leukotriene B(4) (LTB(4)) concentration. The effect on ischemic stroke was evaluated by logistic regression. RESULTS: Three genetic variants were identified, including a mutation (-519 G > A), an insertion and deletion polymorphisms (-581_582 Ins A) and a single nuclear polymorphisms (-946 A > G). Association study showed that the II genotype of -581_582 Ins A was significantly associated with ischemic stroke of a large artery atherosclerosis (OR = 3.50, 95% CI = 1.93-6.36, p = 0.0002) and undetermined etiology (OR = 3.66, 95% CI = 1.92-6.94, p = 0.0006). No significant association was found between the -519 GA genotype (OR = 0.35, 95% CI = 0.02-5.88, p = 0.46), -946 AG genotype (OR = 1.35, 95% CI = 0.85-2.16, p = 0.21) and ischemic stroke. There was no significant difference in serum LTB(4) concentration between cases (n = 40) and controls (n = 40) (log serum LTB(4) of cases vs. controls: 2.67 ± 0.14 vs. 2.73 ± 0.18 pg/ml, p = 0.10). However, the serum LTB(4) concentration was significantly higher in participants with the II genotype of -581_582 Ins A (n = 12) than that of participants with the DD genotype (n = 68) (log serum LTB(4) of participants with II genotype vs. DD genotype: 2.82 ± 0.18 vs. 2.68 ± 0.15 pg/ml, p = 0.01). CONCLUSION: The -581_582 Ins A polymorphism might be a novel genetic risk factor for ischemic stroke in a north Chinese Han population. Further studies on molecular mechanism are warranted. SN - 1421-9786 UR - https://www.unboundmedicine.com/medline/citation/21893978/Genetic_variants_in_the_promoter_region_of_the_ALOX5AP_gene_and_susceptibility_of_ischemic_stroke_ L2 - https://www.karger.com?DOI=10.1159/000330341 DB - PRIME DP - Unbound Medicine ER -