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Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for NAFLD have been hampered by the relative paucity of human data from gold-standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide association studies using NAFLD surrogate phenotypes have been used, but only a small number of loci have been identified to date. In this study, we combined GWAS of NAFLD composite surrogate phenotypes with genetic colocalization studies followed by functional in vitro screens to identify bona fide causal genes for NAFLD. Approach & Results: We used the UK Biobank to explore the associations of our novel NAFLD score, and genetic colocalization to prioritize putative causal genes for in vitro validation. We created a functional genomic framework to study NAFLD genes in vitro using CRISPRi. Our data identify VKORC1, TNKS, LYPLAL1 and GPAM as regulators of lipid accumulation in hepatocytes and suggest the involvement of VKORC1 in the lipid storage related to the development of NAFLD. Conclusions: Complementary genetic and genomic approaches are useful for the identification of NAFLD genes. Our data supports VKORC1 as a bona fide NAFLD gene. We have established a functional genomic framework to study at scale putative novel NAFLD genes from human genetic association studies.
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Sexually transmitted infections (STIs) represent a public health problem worldwide. The aim of this study was to investigate the prevalence of curable STIs caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum in female sex workers in a population from Zulia State, Venezuela. Seventy eight (78) women attended a health monitoring sanitary controls were evaluated, and PCR amplification assays were used to detect the three microorganisms in endocervical samples. In 33.3% of the samples, at least one microorganism was detected: U. urealyticum was found more frequently (25.6%), followed by N. gonorrhoeae (18%), and C. trachomatis (12.8%). A significant association between N. gonorrhoeae and C. trachomatis was found (p <0.0001). STIs cases represented 42.9% and 28% for symptomatic and asymptomatic groups, respectively. In the symptomatic group, N. gonorrhoeae was 2.4 times (28.6%) more frequent than in the asymptomatic one (12%) (p=0.015), particularly associated with mucopurulent discharge (p=0.025). No association was found between C. trachomatis (p=0.078), and U. urealyticum (p=0.432) with clinical manifestations. Prevalence of curable STIs in the study population was relatively low compared with other high-risk populations worldwide. The results support the possible association between C. trachomatis and N. gonorrhoeae, therefore, treatment would be indicated against both pathogens when one of them is detected in vulnerable populations.
Las infecciones de transmisión sexual (ITS) representan un problema de salud pública a nivel mundial. El objetivo de este estudio fue investigar la prevalencia de ITS curables causadas por Neisseria gonorrhoeae, Chlamydia trachomatis y Ureaplasma urealyticum en trabajadoras sexuales de una población del estado Zulia, Venezuela. Se evaluaron 78 mujeres que asistieron a jornadas de control sanitario y se utilizaron ensayos de amplificación por PCR para detectar los tres microorganismos en muestras endocervicales. En 33,3% de las muestras, se detectó al menos un microorganismo: U. urealyticum fue encontrado con mayor frecuencia (25,6%), seguido de N. gonorrhoeae (18%) y C. trachomatis (12,8%). Se encontró asociación significativa entre N. gonorrhoeae y C. trachomatis (p<0,0001). Los casos de ITS representaron porcentajes de 42% y 28% para los grupos sintomático y asintomático, respectivamente. N. gonorrhoeae fue 2,4 veces más frecuente en el grupo sintomático (28,6%) que en el asintomático (12%) (p=0,015), particularmente asociado con secreción mucopurulenta (p=0,025). No se encontró asociación entre C. trachomatis (p=0,078) y U. urealyticum (p=0,432) con manifestaciones clínicas. La prevalencia de ITS de la población en estudio fue relativamente baja comparada con otras poblaciones de alto riesgo a nivel mundial. Los resultados apoyan la posible asociación entre C. trachomatis y N. gonorrhoeae, por lo tanto se debería considerar el tratamiento contra ambos patógenos, cuando uno de ellos sea detectado en poblaciones vulnerables.
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Objective This study was aimed at investigating the frequency of infection by Cp. psittaci and determining its genotype in individuals at potential risk of exposure to the bacteria. Methodology The study involved 170 individuals: a risk group (n= 96) and a low-risk control group (n=74). Cp. psittaci was detected and genotyped by single-tube nested PCR and ompA gene sequencing. Results Eight (8.3 %) positive cases were detected in the risk group and 1 (1.4 %) in the control group (p<0.04). Cp. psittaci was found in 16.7 % of pigeons' fecal samples. Cp. psittaci infection with was more frequent in symptomatic (17.7 %) than asymptomatic (6.3 %) individuals in the risk group. Analysing the genomes isolated from human and bird specimens revealed the presence of genotype B. Conclusion The presence of Cp. psittaci genotype B in the population being evaluated could have been attributed to zoonotic transmission from pigeons to humans, an underestimated potential public health problem in Venezuela requiring the health authorities' involvement.
Objetivo El objetivo de este estudio fue investigar la frecuencia de infecciones por Cp. psittaci y determinar su genotipo en individuos con potencial riesgo de exposición a la bacteria. Metodología Se incluyeron 170 individuos, un grupo de riesgo (n=96) y un grupo control (n=74). La detección y genotipificación de Cp. psittaci se llevó a cabo por PCR anidada y secuenciación del gen ompA. Resultados Se detectaron ocho (8,3 %) casos positivos en el grupo de riesgo y 1 (1,35 %) en el grupo control (p<0,04). Cp. psittaci fue detectada en 16,7 % muestras fecales de palomas. En el grupo de riesgo, la frecuencia de infección por Cp. psittaci fue 17,7 % en individuos sintomáticos y 6,3% en asintomáticos. El análisis de los genomas aislados de muestras humanas y aves, revelaron la presencia del genotipo B. Conclusión La presencia de Cp. psittaci genotipo B en la población evaluada podría ser atribuida a transmisión zoonótica de palomas a humanos, un potencial problema de salud pública en nuestra región que requiere la intervención de autoridades sanitarias.