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71.
TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples 总被引:6,自引:0,他引:6
Lazarus R Raby BA Lange C Silverman EK Kwiatkowski DJ Vercelli D Klimecki WJ Martinez FD Weiss ST 《American journal of respiratory and critical care medicine》2004,170(6):594-600
TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed asthma was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to asthma risk. 相似文献
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Giuseppe Tagariello Rosanna Di Gaetano Roberto Sartori Daniela Zanotto Donata Belvini Paolo Radossi Renzo Risato Giovanni Roveroni Roberta Salviato Cristina Tassinari Nunzio Toffano 《Trasfusione del sangue》2009,7(2):111-116
Background
It is not rare to observe in blood donors a level of haematocrit (Hct) above or close to the highest normal limit. In the case of blood donors the diagnosis and clinical evaluation of this alteration may be complicated by regular blood donations that can mask an underlying disease such as polycythaemia vera. Recently a single acquired mutation in the Janus kinase 2 gene (JAK2) on chromosome 9 was identified and it was found that the incidence of this mutation was high in patients with polycythaemia vera.Material and Methods
From the January 1, 2006 to December 31, 2006 all consecutive donors with a Hct above 50% if males (n=84) and 46% if females (n=19) underwent JAK2 mutation analysis. Seventy-nine donors (59 males and 20 females) whose Hct was normal at their last blood donation were randomly selected and used as controls.Results
Among the group of blood donors with a high Hct, we identified one donor who was positive for the JAK2 mutation. This man had a Hct of 50.6% at his last donation, while his average Hct in the preceding year was 51.7%. The prevalence of the JAK2 mutation could be estimated to be 1%, 0.6% or 0.02% in the three different populations considered: donors with a Hct level above the upper limit of normal, all tested donors or the entire donor cohort attending our transfusion service, respectively.Conclusions
The present study suggests that apparently healthy subjects with repeatedly high levels of Hct may have the acquired mutation in JAK2. Laboratory screening tests for JAK2 may be offered to blood donors at transfusion services with expertise in molecular genetics. 相似文献74.
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Pinzani P Lind K Malentacchi F Nesi G Salvianti F Villari D Kubista M Pazzagli M Orlando C 《Human pathology》2008,39(10):1474-1482
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Giulio Nicita Donata Villari Simone Caroassai Grisanti Michele Marzocco Vincenzo Li Marzi Alberto Martini 《European urology》2017,71(1):133-138