RESUMO
BACKGROUND AND PURPOSE: Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication. METHODS: Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age<60 years) consisting of 3676 cases and 21118 non-stroke controls from 6 case-control studies. Lastly, we determined if the replicated SNPs also associated with older-onset ischemic stroke in the METASTROKE data-base. RESULTS: Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. CONCLUSION: PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.
Assuntos
Isquemia Encefálica/genética , Receptor de Proteína C Endotelial/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Trombomodulina/genética , Adolescente , Adulto , Negro ou Afro-Americano/genética , Idade de Início , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , População Branca/genética , Adulto JovemRESUMO
OBJECTIVES: The objective of this study was to evaluate patients with VL from the city of Tabuk, Kingdom of Saudi Arabia, with particular reference to the possibility that a focus of VL exists in the North West Province of Saudi Arabia, an area where it had not previously been reported. SETTING: North West Armed Forces Hospital, Tabuk, Saudi Arabia. DESIGN: Retrospective evaluation of all cases of infantile visceral leishmaniasis diagnosed in Tabuk, Saudi Arabia between 1989 and 1994. RESULTS: 5 cases of infantile visceral leishmaniasis were reviewed. In four cases, no evidence of travel outside Tabuk could be identified, suggesting primary infection by viscerotropic Leishmanial organisms in this area of Saudi Arabia. CONCLUSIONS: Visceral leishmaniasis has been identified in an area previously not considered endemic for L. donovani. This observation may indicate either, a previously unrecognized focus of L. donovani or provide further evidence of a changing pathogenic role for L. tropica.
