[en] Introduction : The tryptase is a serine protease related to the trypsin . The term tryptase comprising at least four different proteases : ? , ? , ? and ? , which differ as to its enzymatic properties . The functions of this protein have not been fully elucidated , although it has been implicated in inflammatory processes , protection against infection and other immunological phenomena. The structure of this protein is tetrameric and genes encoding them are grouped in the position 16p13.3 . Described mechanisms of transcriptional and post- transcriptional regulation able to modify individual expression levels. Furthermore, along the TPSAB1se gene have been described several polymorphisms. The hypothesis is based on variations in the sequence of the gene could affect TPSAB1 tryptase levels and function . Besides identifying such changes could help explain the mechanisms by which these changes occur tryptase expression and relationship to specific phenotypes . Material and Methods : We studied 135 controls tryptase levels below 11.4 mg / L and 167 patients diagnosed with asthma of allergic origin . In addition, 4 members of a family with high levels of tryptase were included : patient testing ( with variegated clinical and mastocytosis in a discarded ) and two daughters and a sister of that , with high levels of tryptase , but asymptomatic, and husband of patient testing , which showed normal levels of tryptase and was also asymptomatic. The samples were amplified from DNA by PCR with oligonucleotides as described previously , for a more precise analysis of representative samples cloned . The frequencies of the polymorphic sites was estimated . RFLP (polymorphism 363C > T that can distinguish between the ? and ? forms ) was analyzed. The promoter by PCR with oligonucleotides designed with the Primer3 software amplified. The impact of various SNP was studied by in silico analysis. The protein sequence was analyzed by in silico analysis . Moreover, expression analysis was performed by RT -PCR in patients with elevated tryptase . Results and conclusions: We have studied the gene TPSAB1 , analyzing and describing polymorphisms previously described 19 new polymorphisms in the gene region comprised between exon 5 and exon 6, studied in depth to be highly polymorphic , another SNP has been described in intron 1. No significant differences were found between the group of patients and controls in relation to the presence of the ? form or its absence , although lower tryptase levels were observed in those individuals with this form , which may be related to its constitutive secretion. The molecular analysis of TPSAB1 gene family study has detected a pattern binding factors specific transcription in the promoter region of the proband clearly differentiated from controls and could be related to the elevated expression of mRNA testing patient . Detected between transcription factors and MAZ MITF include those described involved in controlling the expression of tryptase in murine models. Several polymorphisms have been identified in the gene sequence of the patient tryptase testing modifying the amino acid encoded at positions with implications for both stability and phosphorylation motifs . These changes could be related to the phenotype of the patient with elevated tryptase . We describe for the first time the existence of a disease entity for which we suggest the term hipertriptasemia family , in which different members of the same family have elevated levels of tryptase without mastocytosis.

[es] Introducci?n: La triptasa es una serin-proteasa relacionada con la tripsina. El t?rmino triptasa comprende al menos cuatro proteasas diferentes: ?, ?, ? y ?, que presentan diferencias en cuanto a sus propiedades enzim?ticas. Las funciones de esta prote?na no han sido completamente dilucidadas, aunque se ha implicado en fen?menos inflamatorios, protecci?n contra la infecci?n y otros fen?menos inmunol?gicos. La estructura de esta prote?na es tetram?rica y los genes que las codifican se encuentran agrupados en la posici?n 16p13.3. Se han descrito mecanismos de regulaci?n transcripcional y post-transcripcionales capaces de modificar los niveles individuales de expresi?n. Adem?s, a lo largo del gen TPSAB1se han descrito varios polimorfismos . La hip?tesis se basa en que las variaciones en la secuencia del gen TPSAB1 podr?a afectar a los niveles de triptasa y funci?n. Adem?s la identificaci?n de tales modificaciones podr?a ayudar a explicar los mecanismos por los que dichos cambios en la expresi?n de triptasa ocurren y la relaci?n con fenotipos espec?ficos. Material y M?todos: Se han estudiado 135 controles con niveles de triptasa inferiores a 11,4 ?g/L y 167 pacientes diagnosticados de asma de origen al?rgico. Adem?s se incluyeron 4 miembros de una familia con niveles elevados de triptasa: la paciente probando (con cl?nica abigarrada y en la que se descart? una mastocitosis) y dos hijas y una hermana de aquella, con niveles elevados de triptasa, pero asintom?ticas, y el marido de la paciente probando, que presentaba niveles normales de triptasa y se encontraba tambi?n asintom?tico. Las muestras fueron amplificadas a partir de ADN por reacci?n de PCR con oligonucle?tidos previamente descritos; para un an?lisis m?s preciso se clonaron muestras representativas. Se estimaron las frecuencias de los sitios polim?rficos. Se analiz? el RFLP (polimorfismo 363C>T que permite distinguir entre la forma ? y ?). Se amplific? el promotor mediante PCR con oligonucle?tidos dise?ados con el software primer3. Se estudi? el impacto de los distintos SNP por medio de an?lisis in silico. La secuencia proteica fue analizada por an?lisis in silico. Adem?s, el an?lisis de expresi?n se llev? a cabo mediante RT-PCR en los pacientes con triptasa elevada. Resultados y conclusiones: Se ha estudiado el gen TPSAB1, analiz?ndose polimorfismos previamente descritos y describi?ndose 19 nuevos polimorfismos en la regi?n del gen comprendida entre el ex?n 5 y ex?n 6, estudiada en profundidad por ser altamente polim?rfica; otro SNP ha sido descrito en el intr?n 1. No se han encontrado diferencias estad?sticamente significativas entre el grupo de pacientes y controles en relaci?n a la presencia de la forma ? o la ausencia de ?sta, si bien se observaron niveles de triptasa inferiores en aquellos individuos con esta forma, lo que se puede relacionar con su secreci?n constitutiva. En el an?lisis molecular del gen TPSAB1 en la familia de estudio se ha detectado un patr?n de uni?n de factores de transcripci?n espec?fico en la regi?n promotora del probando claramente diferenciado del de los controles, y que podr?a estar relacionado con la elevada expresi?n de ARNm de la paciente probando. Entre los factores de transcripci?n detectados destacan MITF y MAZ que se han descrito implicados en el control de la expresi?n de triptasa en modelos m?ridos. Se han detectado varios polimorfismos en la secuencia del gen de la triptasa de la paciente probando que modifican el amino?cido codificado en posiciones con implicaciones tanto en la estabilidad como en los motivos de fosforilaci?n. Estas modificaciones podr?an estar relacionadas con el fenotipo de la paciente con niveles elevados de triptasa. Describimos por primera vez la existencia de una entidad nosol?gica para la que sugerimos el t?rmino hipertriptasemia familiar, en la que distintos miembros de una misma familia presentan niveles elevados de triptasa sin mastocitosis.