RESUMEN
BACKGROUND: Pneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients. METHODS: Seventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017. RESULTS: The NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = - 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = - 0.54, p = 0.01, and beta = - 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = - 0.83, p = 0.03; beta = - 1, p = 0.02 and beta = 1.07, p = 0.008, respectively). CONCLUSIONS: A genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.
RESUMEN
Se realizó una valoración integral prospectiva de los 149 adultos mayores residentes en el Hogar de Ancianos "Pedro Luis Almaguer" del municipio Banes, en los meses correspondientes a enero y febrero de 1999. Se realizó un conversatorio explicándoles en qué consistía la investigación, y se obtuvo el consentimiento de dichos gerontes objeto de estudio. Los datos se sacaron de las historias clínicas de los adultos mayores residentes en la institución. De los casos estudiados el 34,2 (por ciento) corresponde al sexo femenino y el 65,8 (por ciento) al masculino; al valorar las afecciones encontramos como cifra representativa que el 15,3 (por ciento) padece de hipertensión arterial. Al estudiar el estado mental podemos observar que el 26,8 (por ciento) padece de demencia senil; al analizar el estado físico, aparece como cifra representativa que el 6,7 (por ciento) de los adultos mayores en nuestra investigación son ciegos, de los gerontes estudiados el 94,60 (por ciento) posee una relación aceptable, el 18,1 (por ciento) de los adultos mayores de nuestra institución necesitan de la ayuda de la fisioterapeuta y el personal de Enfermería para la realización de los ejercicios físicos. Al realizar la valoración del estado nutricional en nuestros gerontes institucionalizados tuvimos como cifra relevante que el 84,5 (por ciento) son normopesos(AU)
