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CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke.
Pharmacogenomics. 2010 Jun; 11(6):763-72.P

Abstract

AIMS

To find genetic predictors of reocclusion after successful fibrinolytic therapy during the acute phase of ischemic stroke.

PATIENTS & METHODS

This was a case-case prospective study analyzing 236 polymorphisms in a cohort of 222 patients treated with tissue plasminogen activator, from which 16 patients suffered a reocclusion event (7.2%). A predictive scale was generated using independent polymorphisms with a dominant/recessive model and tandem occlusion, weighted by their beta-coefficients in logistic regression.

RESULTS

Using a dominant/recessive model, the rs1800801 SNP from the MGP gene (odds ratio [OR]: 15.25; 95% CI: 2.23-104.46; adjusted p = 0.006) and the rs1883832 SNP from CD40 gene (OR: 0.077; 95% CI: 0.009-0.66; adjusted p = 0.019) were independently associated with reocclusion after logistic regression adjustment by clinical predictors. In an additive model, only the rs1883832 SNP (OR: 4.43; 95% CI: 1.62-12.15; adjusted p = 0.004) was related to reocclusion occurrence. The predictive model that was generated stratified the reocclusion risk from less than 1% to more than 70%. Reocclusions were associated with neurological worsening at 24 h (patients with reocclusion: 26.7%, versus patients without reocclusion: 4.9%; p = 0.002), as it was seen for MGP -7A>G (AA: 17.2% vs AG+GG: 4.5%; p = 0.027), but not for CD40 1C>T (CC: 4.5% vs CT+TT: 7.7%; p = 0.565). There was an association between CD40 -1C>T genotype and CD40 transcriptional activity in peripheral blood mononuclear cells (median expression values TT: 65.75%, CT: 70.80%, CC: 96.00%; p = 0.023). However, CD40 soluble fraction was not a useful biomarker of reocclusion status.

CONCLUSION

An association was found between MGP -7A>G and CD40 -1C>T polymorphisms, and reocclusion risk. The predictive scale that was generated permits the stratification of patients by their reocclusion risk with higher accuracy than clinical parameters alone.

Authors+Show Affiliations

Neurovascular Research Laboratory, Institut de Recerca, Hospital Vall d'Hebron, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20504251

Citation

del Río-Espínola, Alberto, et al. "CD40-1C>T Polymorphism (rs1883832) Is Associated With Brain Vessel Reocclusion After Fibrinolysis in Ischemic Stroke." Pharmacogenomics, vol. 11, no. 6, 2010, pp. 763-72.
del Río-Espínola A, Fernández-Cadenas I, Rubiera M, et al. CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke. Pharmacogenomics. 2010;11(6):763-72.
del Río-Espínola, A., Fernández-Cadenas, I., Rubiera, M., Quintana, M., Domingues-Montanari, S., Mendióroz, M., Fernández-Morales, J., Giralt, D., Molina, C. A., Alvarez-Sabín, J., & Montaner, J. (2010). CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke. Pharmacogenomics, 11(6), 763-72. https://doi.org/10.2217/pgs.10.44
del Río-Espínola A, et al. CD40-1C>T Polymorphism (rs1883832) Is Associated With Brain Vessel Reocclusion After Fibrinolysis in Ischemic Stroke. Pharmacogenomics. 2010;11(6):763-72. PubMed PMID: 20504251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke. AU - del Río-Espínola,Alberto, AU - Fernández-Cadenas,Israel, AU - Rubiera,Marta, AU - Quintana,Manuel, AU - Domingues-Montanari,Sophie, AU - Mendióroz,Maite, AU - Fernández-Morales,Jessica, AU - Giralt,Dolors, AU - Molina,Carlos A, AU - Alvarez-Sabín,José, AU - Montaner,Joan, PY - 2010/5/28/entrez PY - 2010/5/28/pubmed PY - 2010/10/20/medline SP - 763 EP - 72 JF - Pharmacogenomics JO - Pharmacogenomics VL - 11 IS - 6 N2 - AIMS: To find genetic predictors of reocclusion after successful fibrinolytic therapy during the acute phase of ischemic stroke. PATIENTS & METHODS: This was a case-case prospective study analyzing 236 polymorphisms in a cohort of 222 patients treated with tissue plasminogen activator, from which 16 patients suffered a reocclusion event (7.2%). A predictive scale was generated using independent polymorphisms with a dominant/recessive model and tandem occlusion, weighted by their beta-coefficients in logistic regression. RESULTS: Using a dominant/recessive model, the rs1800801 SNP from the MGP gene (odds ratio [OR]: 15.25; 95% CI: 2.23-104.46; adjusted p = 0.006) and the rs1883832 SNP from CD40 gene (OR: 0.077; 95% CI: 0.009-0.66; adjusted p = 0.019) were independently associated with reocclusion after logistic regression adjustment by clinical predictors. In an additive model, only the rs1883832 SNP (OR: 4.43; 95% CI: 1.62-12.15; adjusted p = 0.004) was related to reocclusion occurrence. The predictive model that was generated stratified the reocclusion risk from less than 1% to more than 70%. Reocclusions were associated with neurological worsening at 24 h (patients with reocclusion: 26.7%, versus patients without reocclusion: 4.9%; p = 0.002), as it was seen for MGP -7A>G (AA: 17.2% vs AG+GG: 4.5%; p = 0.027), but not for CD40 1C>T (CC: 4.5% vs CT+TT: 7.7%; p = 0.565). There was an association between CD40 -1C>T genotype and CD40 transcriptional activity in peripheral blood mononuclear cells (median expression values TT: 65.75%, CT: 70.80%, CC: 96.00%; p = 0.023). However, CD40 soluble fraction was not a useful biomarker of reocclusion status. CONCLUSION: An association was found between MGP -7A>G and CD40 -1C>T polymorphisms, and reocclusion risk. The predictive scale that was generated permits the stratification of patients by their reocclusion risk with higher accuracy than clinical parameters alone. SN - 1744-8042 UR - https://www.unboundmedicine.com/medline/citation/20504251/CD40_1C>T_polymorphism__rs1883832__is_associated_with_brain_vessel_reocclusion_after_fibrinolysis_in_ischemic_stroke_ L2 - https://www.futuremedicine.com/doi/10.2217/pgs.10.44?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -