Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations

BACKGROUND: The global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations. RESULTS: DNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008). CONCLUSIONS: These results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.Fil: Pontoriero, Ana Cecilia. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hulaniuk, María Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fortuny, Lisandro. Hospital Italiano; ArgentinaFil: Burgos Pratx, Leandro. Hospital Italiano; ArgentinaFil: Frías, Analía. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Torres, Oscar. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Nuñez, Félix. Hospital Italiano; ArgentinaFil: Gadano, Adrián. Hospital Italiano; ArgentinaFil: Argibay, Pab lo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentin

Clinical utility of pharmacogenomics in the management of hepatitis C

Hepatitis C virus (HCV) was identified for the first time more than 20 years ago. Since then, several studies have highlighted the complicated aspects of this viral infection in relation to its worldwide prevalence, its clinical presentation, and its therapeutic response. Recently, two landmark scientific breakthroughs have moved us closer to the successful eradication of chronic HCV infection. First, response rates in treatment-naïve patients and in prior non-responders to pegylated-interferon-α and ribavirin therapy are increasing as a direct consequence of the development of direct-acting antiviral drugs. Secondly, the discovery of single-nucleotide polymorphisms near the interleukin 28B gene significantly related to spontaneous and treatment-induced HCV clearance represents a milestone in the HCV therapeutic landscape. The implementation of this pharmacogenomics finding as a routine test for HCV-infected patients has enhanced our understanding of viral pathogenesis, has encouraged the design of ground-breaking antiviral treatment regimens, and has become useful for pretreatment decision making. Nowadays, interleukin 28B genotyping is considered to be a key diagnostic tool for the management of HCV-infected patients and will maintain its significance for new combination treatment schemes using direct-acting antiviral agents and even in interferon-free regimens. Such pharmacogenomics insights represent a challenge to clinicians, researchers, and health administrators to transform this information into knowledge with the aim of elaborating safer and more effective therapeutic strategies specifically designed for each patient. In conclusion, the individualization of treatment regimens for patients with hepatitis C, that may lead to a universal cure in future years, is becoming a reality due to recent developments in biomarker and genomic medicine. In light of these advances, we review the scientific evidence and clinical implications of recent findings related to host genetic factors in the management of HCV infection.Fil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hulaniuk, María Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Redal, María Ana. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Inferring the genetic structure of Northwestern Argentina by uniparental SNP typing

The genetic background of South American populations is the result of four major genetic admixture events. To investigate the maternal and paternal lineages, we analyzed mitochondrial DNA (mt-DNA): A2, B2, C, D1; and Y-chromosome (Y-DNA) haplogroups (hg): R1b1b2, Q1a3a, G2a, I, J2, E1b1b, based on SNP typing by real time PCR and high-resolution melting analysis. Individuals from Northwestern Argentina (NWA) (n = 187) were studied and compared with Buenos Aires Metropolitan Area´s inhabitants (BUE) (n = 107) and recently arrived immigrants from Bolivia (BOL) (n = 100), Paraguay (PAR) (n = 54) and Peru (PER) (n = 52). Native American (NA) mt-DNA hgs were the most frequent in all regions (89,8%?98,1%), except for BUE (43%), being B2 the most prevalent (42,6%?58% versus 8,4% in BUE). Regarding Y-DNA hg, a greater contribution of the non-Native American (non-NA) lineage was found in all populations (61,5%?99%), except for BOL (32,7%). Moreover, the most frequent hg observed were R1b1b2 (50% PAR, 46,6% BUE, 30,2% NWA) and Q1a3a (67,3% BOL, 38,5% PER). A high percentage of NA mt-DNA/non-NA Y-DNA was represented (53,8%?63,5%), excepting BUE (41,7%) and BOL (26,9%). Data obtained is consistent with historical information underscoring the complex genetic ancestry of melting pot countries. The results offer additional tools for forensic investigation; molecular epidemiological and anthropological studies.Fil: Castagnola, María Josefina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cano, Hortensia. Provincia de Santa Cruz. Poder Judicial. Laboratorio Regional de Investigación Forense; ArgentinaFil: Hulaniuk Wolaniuk, Maria Laura. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Distribution of genetic polymorphisms associated to hepatitis c virus (HCV) antiviral response in a multiethnic and admixed population

2 p.Single-nucleotide polymorphisms (SNPs) near IL28B and ITPA genes have been described as predictors of response to antiviral treatment and ribavirin induced-hemolytic anemia in HCV patients, respectively. The prevalence of these polymorphisms differs among ethnic groups; however, there is a paucity of information about South American populations. Hence, the aim of this study was to determine the prevalence of these SNPs in the healthy population of different ethnic groups residing in Argentina.http://www.viral-hep.org/default.aspxFil: Thinks, Julieta. Hospital Italiano de Buenos Aires. Instituto de Ciencias Básicas y Medicina Experimental; Argentina.Fil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Fil: Hulaniuk, María Laura. Hospital Italiano de Buenos Aires. Instituto de Ciencias Básicas y Medicina Experimental; Argentina.Fil: Burgos Pratx, Leandro. Servicio de Medicina Transfusional; Argentina.Fil: Ré, Viviana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología Dr. José María Vanella; Argentina.Fil: Fortuny, Lisandro. Servicio de Medicina Transfusional; Argentina.Fil: Frías, Analía. Servicio de Medicina Transfusional; Argentina.Fil: Torres, Oscar. Servicio de Medicina Transfusional; Argentina.Fil: Nuñez, Félix. Servicio de Medicina Transfusional; Argentina.Fil: Gadano, Adrián. Servicio de Hepatología; Argentina.Fil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Fil: Flichman, Diego Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Otras Ciencias de la Salu

Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population

Background: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. Objectives: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population. Study design: A total of 101 HIV-1 infected subjects, 93 Kaposi´s Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. Results: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. Conclusions: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.Fil: Hulaniuk Wolaniuk, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Mojsiejczuk, Laura Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular;Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Remondegui, Carlos. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Zapiola, Inés. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Ferro, María Verónica. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Ajalla, Claudia. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Blejer, Jorgelina L.. Fundación Hemocentro Buenos Aires; ArgentinaFil: Alter, Adriana. Fundación Hemocentro Buenos Aires; ArgentinaFil: Acevedo, María Elina. Fundación Hemocentro Buenos Aires; ArgentinaFil: Rodríguez, Eulalia. Fundación Hemocentro Buenos Aires; ArgentinaFil: Fernández, Roberto. Fundación Hemocentro Buenos Aires; ArgentinaFil: Bartoli, Sonia. Gobierno de la Provincia de San Salvador de Jujuy. Hospital “Pablo Soria”. Servicio de Hemoterapia; ArgentinaFil: Volonteri, Victoria. Hospital Italiano; ArgentinaFil: Kohan, Dana. Centro Privado de Patología; ArgentinaFil: Elsner, Boris. Centro Privado de Patología; ArgentinaFil: Bürgesser, María Virginia. Centro de Anatomía Patológica y Citopatología; ArgentinaFil: Reynaud, Ana Laura. Laboratorio de Patología y Citopatología; ArgentinaFil: Sánchez, Marisa. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: González, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Garcia Rivello, Hernan Jorge. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Corach, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Caputo, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin