Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients.

BACKGROUND & AIMS: Genetic variation in the interleukin 28B (IL28B) gene has been associated with the response to interferon-alfa/ribavirin therapy in hepatitis C virus (HCV) genotype 1-infected patients. The importance of three IL28B single nucleotide polymorphisms (rs8099917, rs12980275 and rs12979860) for HCV genotype 2/3-infected patients is unknown. METHODS: In patients with chronic hepatitis C genotype 2/3 (n=267), IL28B host genotypes (rs8099917, rs12980275 and rs12979860) were analyzed for associations with sustained virologic response (SVR) to antiviral therapy with (pegylated) interferon-alfa and ribavirin and with respect to epidemiological, biochemical, and virological parameters. For comparison, hepatitis C genotype 1 patients (n=378) and healthy controls (n=200) were included. RESULTS: The rs12979860 CC genotype, lower age, and genotype 2 were significantly associated with SVR in HCV genotype 2/3-infected patients (p=0.01, p=0.03 and p=0.03, respectively). No association was observed for rs8099917 and rs12980275. In addition, an SVR in patients with rapid virologic response (RVR) was associated with the rs12979860 CC genotype (p=0.05), while for non-RVR no association was found. Furthermore, a significant association with a higher baseline viral load was observed for all three IL28B genotypes in genotype 1/2/3-infected patients. Finally, increasing frequencies of the rs12979860 CC genotypes were observed in genotype 1- (33.9%), genotype 3- (38.9%), and genotype 2-infected (51.9%) patients in comparison with healthy controls (49.0%) (p<0.01). CONCLUSIONS: In genotype 2/3-infected patients, rs12979860 was significantly associated with SVR. The frequency of the rs12979860 CC genotype is lower in HCV genotype 1 vs. genotype 2/3 patients. All major IL28B genotypes are associated with HCV-RNA concentration.

Variabilidade espacial de características de solos na região do Planalto Médio, RS: I. análise da variância por amostragem aninhada

A variabilidade espacial das características cor do solo, conteúdo de argila, pH e resistência à penetração foi avaliada em sete glebas com solos fortemente intemperizados e intensamente cultivados, na região do Planalto Médio (RS), por meio da análise da variância pelo método de amostragem aninhada, com o objetivo de determinar sua homogeneidade e estimar o intervalo indicado para efetuar amostragens sistemáticas de solos. Perfis representativos foram caracterizados e classificados nessas glebas. O trabalho de campo foi realizado em agosto-novembro de 1989. Latossolos vermelho-escuro e amarelo distróficos e álicos ocorrem nas glebas estudadas. As características analisadas, exceto o valor da cor e o pH na camada de 60-80 cm, apresentaram grande variabilidade. A contribuição à variância total aumentou relativamente pouco nos intervalos de amostragem de 50 a 600 m. De 600 m à distância entre glebas (> 3000 m), ocorreu grande incremento na variância, indicando que intervalos de amostragem de 600 m ou maiores são suficientes para o estudo de características relacionadas à gênese do solo. Variâncias em características químicas e físicas, relacionadas ao manejo do solo, persistirão dentro de delineamentos produzidos nesse intervalo de amostragem. Os mesmos esquemas com intervalos de amostragem de 50 m não poderão resolver tais variâncias.

Variabilidade espacial de características de solos na região do Planalto Médio, RS: II. análise da semivariância e da variância

A variabilidade espacial das características de solos da região do Planalto Médio (RS) foi estudada em seis glebas cultivadas com soja, por meio das análises da semivariância e da variância, em amostragem sistemática, para confirmar e detalhar resultados obtidos por análise da variância por amostragem aninhada; estimar a variância nas características dentro de unidades de mapeamento de solos e a extensão do uso de mapas de solos para avaliação de terras. O trabalho de campo foi realizado de dezembro de 1989 a março de 1990. Os resultados confirmam que características de solos dependentes de processos pedogenéticos mostram interdependência espacial de 500 m ou mais, porém a variância de características afetadas pelo manejo persistirá em espaçamentos menores. Outrossim, que qualidades da terra, como disponibilidade de nutrientes, não podem ser extraídas apenas de mapas de solos e que métodos alternativos de amostragem devem ser testados para amenizar o efeito negativo da variância de características a curtas distâncias na qualidade de mapas pedológicos.

Helsingin äitikirkko

Pentti Lempiäinen

Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development

BACKGROUND: Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.

Variability of apparently homogeneous soilscapes in São Paulo state, Brazil: I. spatial analysis

The spatial variability of strongly weathered soils under sugarcane and soybean/wheat rotation was quantitatively assessed on 33 fields in two regions in São Paulo State, Brazil: Araras (15 fields with sugarcane) and Assis (11 fields with sugarcane and seven fields with soybean/wheat rotation). Statistical methods used were: nested analysis of variance (for 11 fields), semivariance analysis and analysis of variance within and between fields. Spatial levels from 50 m to several km were analyzed. Results are discussed with reference to a previously published study carried out in the surroundings of Passo Fundo (RS). Similar variability patterns were found for clay content, organic C content and cation exchange capacity. The fields studied are quite homogeneous with respect to these relatively stable soil characteristics. Spatial variability of other characteristics (resin extractable P, pH, base- and Al-saturation and also soil colour), varies with region and, or land use management. Soil management for sugarcane seems to have induced modifications to greater depths than for soybean/wheat rotation. Surface layers of soils under soybean/wheat present relatively little variation, apparently as a result of very intensive soil management. The major part of within-field variation occurs at short distances (< 50 m) in all study areas. Hence, little extra information would be gained by increasing sampling density from, say, 1/km² to 1/50 m². For many purposes, the soils in the study regions can be mapped with the same observation density, but residual variance will not be the same in all areas. Bulk sampling may help to reveal spatial patterns between 50 and 1.000 m.