Genetic analysis of human predisposition to hepatosplenic disease caused by schistosomes reveals the crucial role of connective tissue growth factor in rapid progression to severe hepatic fibrosis.

Schistosome worms inhabit mammalian mesenteric veins. Their eggs cause chronic inflammation, which progresses to periportal fibrosis in 5 to 30% of cases, increasing portal blood pressure and leading to esophageal varices. Episodes of bleeding cause hepatic necrosis and may ultimately lead to hepatic failure and the death of the patient. Schistosome infections can also cause pulmonary hypertension and heart failure. The mechanisms of fibrogenesis and fibrolysis are beginning to be unraveled, but it remains unclear why disease occurs only in certain subjects, as also observed for other types of chronic liver inflammation, as in hepatitis C or B. We summarize here the results that showed that fibrosis progression is determined by a genetic locus on chromosome 6. The CCN2 gene at this locus, encodes CTGF that is a crucial regulator of fibrosis. Two groups of CCN2 polymorphisms independently modulate the progression of hepatic fibrosis. These results were obtained in an Asian population, but were extended to humans living in Africa and South America and are presently tested in liver fibrosis of other etiological origins.

Forma hepatosplênica da esquistossomose mansônica, em relaçäo à composiçäo racial e ao nível sócio-econômico, em Catolândia-Bahia / Hepatosplenic form of schistosomiasis mansoni, in relation to race and socioeconomic level, in Catolândia-Bahia

De 1125 indivíduos, residentes em área hiperendêmica de esquistosomose mansônica, estudou-se a apresentaçäo clínica, relacionada aos grupos raciais (mestiço de índio, branco, mulato-claro, mulato-médio, mulato-escuro e negro) e ao nível sócioeconômico, conforme o somatório de 16 variáveis. Em 229 indivíduos brancos havia 24 (10,5%) com a forma hepatosplênica, significantemente superior, em comparaçäo com 32 (3,6%) dos 896 näo-brancos; entre os grupos raciais negróides ocorreram freqüentemente semelhantes. Os hepatosplênicos apresentaram nível sócio-econômico mais alto e quando, também, brancos, o risco relativo (2,78) foi marcadamente superior

[Hepatosplenic form of schistosomiasis mansoni, in relation to race and socioeconomic level, in Catolândia-Bahia]. / Forma hepatosplênica da esquistossomose mansônica, em relação à composição racial e ao nível sócio-econômico, em Catolândia-Bahia.

Of 1,125 individuals, residents in an area where mansonic schistosomiasis is hyperendemic, were studied regarding the clinical forms correlated to the racial groups (indian mestizo, white, light mullato, medium mullato, dark mullato and negro) and to their socio-economic level according to a set of 16 variables. The white individuals (10.5%) showed a significantly higher incidence of the hepatosplenic forms; in the other racial groups there were similar frequencies, altogether 3.6%. Those with hepatosplenomegaly had a higher socio-economic level and when they also belonged to the white race the relative risk (2.78) was significantly higher.

Coeficiente de endocruzamento em portadores de esquistossomose mansônica / Imbreeding coefficient in carries of Schistosoma mansoni

O coeficiente de endocruzamento (f ou de Wright) foi calculado em 1123 indivíduos de Catolândia, Bahia, área hiperendêmica da esquistossomose mansônica: 148 (13,2%) tinham o coeficiente f > 0. A forma hepatosplênica foi significantemente maior nos indivíduos com f > 0 (26,8%). Nos brancos com f > 0 o risco relativo foi de 14,1; enquanto, nos brancos com f = 0, a freqüência da hepatosplenomegalia näo diferiu dos näo-brancos com f = ou f > 0. Com este coeficiente estimou-se a probabilidade de genes aléticos iguais, com origem em ancestral comum; os resultados reforçam a hipótese da regulaçäo genética na susceptibilidade à forma hepatosplênica da esquistossomose mansônica

[Inbreeding coefficient in carriers of Schistosoma mansoni]. / Coeficiente de endocruzamento em portadores de esquistossomose mansônica.

The coefficient of inbreeding (for Wright) was studied in Catolândia, in the state of Bahia, Brazil, an area considered hyperendemic for manson schistosomiasis in a population of 1,130 inhabitants. The coefficient of inbreeding was estimated for 1,123 individuals it was classified as f greater than 0 in 13.2% (n = 148). In the hepatosplenic group the frequency of f greater than 0 was 26.8%, and in the hepatointestinal group the frequency was 12.5%. The frequency of the hepatosplenic diagnosis in whites who were f = 0 did not differ from that which was observed in the negroid group. These verifications were confirmed by the Woolf's test; the relative risk of the whites, f greater than 0 in acquiring hepatosplenic schistosomiasis was 14.1. These observations reinforce the influence of the genetic component in the development of the hepatosplenic form of the mansons schistosomiasis.