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

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