Kalirin: a novel genetic risk factor for ischemic stroke

Krug, Tiago; Manso, Helena; Gouveia, Luís F.; Sobral, João; Xavier, Joana M.; Albergaria, Isabel Soares de; Gaspar, Gisela; Correia, Manuel; Viana-Baptista, Miguel; Simões, Rita Moiron; Pinto, Amélia Nogueira; Taipa, Ricardo; Ferreira, Carla; Fontes, João Ramalho; Silva, Mário Rui; Gabriel, João Paulo; Matos, Ilda; Lopes, Gabriela Castro; Ferro, José M.; Vicente, Astrid M.; Oliveira, Sofia A.

doi:10.1007/s00439-010-0790-y

Cited by 51 publications

(33 citation statements)

References 34 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, detailed examination of clinical information from the first sample set, which was uniquely available to us, revealed that congenital or early-onset vascular disease was observed in 5 of 7 cases with P2255T (supplementary table S1). Because KALRN may represent a candidate gene for vascular diseases, 31,32 it is tempting to speculate that P2255T may be a potential risk factor for vascular disease.…”

Section: Discussionmentioning

confidence: 99%

Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility

Kushima

Nakamura

Aleksić

et al. 2010

Schizophrenia Bulletin

View full text Add to dashboard Cite

Background: Our genome-wide association study of schizophrenia found association signals at the Kalirin gene (KALRN) and EPH receptor B1 gene (EPHB1) in a Japanese population. The importance of these synaptogenic pathway genes in schizophrenia is gaining independent supports. Although there has been growing interest in rare (<1%) missense mutations as potential contributors to the unexplained heritability of schizophrenia, there are no population-based studies targeting rare (<1%) coding mutations with a larger effect size (eg, OR >1.5) in KALRN or EPHB1. Methods and Results: The present study design consisted of 3 phases. At the discovery phase, we conducted resequencing analyses for all exon regions of KALRN and EPHB1 using a DNA microarray-based method. Seventeen rare (<1%) missense mutations were discovered in the first sample set (320 schizophrenic patients). After the prioritization phase based on frequencies in the second sample set (729 cases and 562 controls), we performed association analyses for each selected mutation using the third sample set (1511 cases and 1517 controls), along with a combined association analysis across all selected mutations. In KALRN, we detected a significant association between schizophrenia and P2255T (OR 5 2.09, corrected P 5 .048, 1 tailed); this was supported in the combined association analysis (OR 5 2.07, corrected P 5 .006, 1 tailed). We found no evidence of association of EPHB1 with schizophrenia. In silico analysis indicated the functional relevance of these rare missense mutations. Conclusion: We provide evidence that multiple rare (<1%) missense mutations in KALRN may be genetic risk factors for schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility

Kushima

Nakamura

Aleksić

et al. 2010

Schizophrenia Bulletin

View full text Add to dashboard Cite

show abstract

“…The ascertainment and collection criteria for study participants, the DNA extraction and genotyping protocols, as well as the statistical analyses have been described in detail previously [5]. The research protocol was approved by the Ethics Committees of participating institutions.…”

Section: Methodsmentioning

confidence: 99%

Replication of the CELSR1 association with ischemic stroke in a Portuguese case-control cohort

et al. 2011

Self Cite

View full text Add to dashboard Cite

“…18,24,25 Wu et al 16 established Kalirin as a signaling protein that specifically promotes Rac1 activation and contributes to VSMC migration downstream of PDGF in vitro. Importantly, the authors demonstrate that decreased Kalirin expression in vivo significantly reduced neointimal formation in a model of arterial endothelial denudation.…”

Section: See Accompanying Article On Page 702mentioning

confidence: 99%