Distribution of CYP2C19*2 and CYP2C19*3 polymorphisms in Venezuelan populations with different admixture.

BACKGROUND: The conquest and colonization of Venezuela generated very heterogeneous populations as a product of admixture; for this reason, the distribution of polymorphisms of the CYP2C19 gene was studied in various Venezuelan populations. METHODS: Two hundred and eighty-one individuals, from three Venezuelan populations with different admixtures, were genotyped for CYP2C19*2 and CYP2C19*3 polymorphisms. Differences between groups were analysed using a chi-square test of heterogeneity and association of allele frequencies with the level of genetic admixture was performed using a principal component analysis (PCA). No significant differences in distribution of alleles, genotypes and phenotypes were found between the populations studied. RESULTS: In Venezuela, high frequencies of the alleles CYP2C19*2 and CYP2C19*3 were found compared with Europeans, Africans and Latin Americans, similar to those reported in Asia. PCA analysis suggested that the presence of alleles CYP2C19*2 and CYP2C19*3 is associated with the indigenous component in the Venezuelan populations studied. CONCLUSIONS: Future studies are needed to confirm this association. High frequencies of intermediate metabolizers (20-38%) and of poor metabolizers (2-7%) were observed, similar to values reported for Asians and higher than those reported for South Americans. This is the first study evaluating CYP2C19 polymorphisms in the Venezuelan general population.

Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome, and mtDNA markers.

The present Venezuelan population is the product of admixture of Amerindians, Europeans, and Africans, a process that was not homogeneous throughout the country. Blood groups, short tandem repeats (STRs), mtDNA, and Y-chromosome markers have been used successfully in admixture studies, but few such studies have been conducted in Venezuela. In this study we aim to estimate the admixture components of samples from two different socioeconomic levels from Caracas, Venezuela's capital city, compare their differences, and infer sexual asymmetry in the European Amerindian union patterns. Gene frequencies for blood groups ABO and Rh (CDE) and for the STRs VWA, F13A01, and FES/FPS and mtDNA and Y-chromosome haplogroups were studied in a sample of 60 individuals living in Caracas, taken from a private clinic (high socioeconomic level), and 50 individuals, also living in Caracas, drawn from a public maternity clinic (low socioeconomic level). The admixture analysis for the five autosomal markers gives a high European component (0.78) and an almost negligible African sub-Saharan component (0.06) for the high socioeconomic level, whereas for the low socioeconomic level the sub-Saharan, European, and Amerindian components were 0.21, 0.42, and 0.36, respectively. Estimates of admixture based on mtDNA and Y-chromosome markers reveal that the Amerindian contribution to these Caracas samples is almost entirely through females, because the Y-chromosome Amerindian and African sub-Saharan chromosomes found in this study were scarce. Our study reveals that the identification of the grandparents' geographic origin is an important methodological aspect to take into account in genetic studies related to the reconstruction of historical events.

Diversidad mitooondrial en el nor-occidente de enezuela. implicaciones para prrobables rutas migratorias prehispániass / Mitochondrial diversity in Northwest Venezuela. Implications for probable prehispanic migratory routes.

La utilidad del ADN mitocondrial (ADNmt) para determinar afinidad genética entre grupos indígenas contemporáneos e inferir sobre migraciones, ha sido demostrada; pero la imposibilidad de estudiar grupos prehispánicos extintos, limita las inferencias sobre migraciones en esa época. El mestizaje en poblaciones neoamericanas ha sido caracterizado por uniones entre hombres europeos y mujeres indígenas, permitiendo detectar en la población contemporánea haplogrupos mitocondriales amerindios que informan sobre poblaciones extintas. Para conocer los linajes femeninos en el occidente de Venezuela, se estudiaron los haplogrupos del ADNmt a partir de RFLP, en una muestra de 193 individuos con antepasados procedentes del occidente de Venezuela, 81 del Estado Lara (Barquisimeto) y 112 de tres pueblos del Estado Falcón (Macu-quita=25, Macanillas=29 y Churuguara=58). Se comparó la distribución de haplogrupos entre las poblaciones y se estimó el mestizaje por línea femenina en ellas. Se comparó la distribución de cuatro haplogrupos indígenas con otras regiones de América. Se observa que en las cuatro poblaciones predominan haplogrupos amerindios, seguidos de los africanos. Al comparar la fracción indígena con el resto de América encontramos que Macanillas, Lara y Churuguara se asemejan a grupos de Amazonas y Suramérica, mientras que Macuquita a Aruba. Esto sugiere una diversidad genética importante en esa zona como probable ruta de paso hacia el sur y el Caribe; además refleja vínculos genéticos importantes entre grupos prehispánicos de Aruba y los de la Península de Paraguaná. Evidencias arqueológicas soportan estos postulados. Se recomienda aumentar la muestra y realizar análisis de secuencias para un nivel mayor de precisión.

Mitocondrial DNA (mtDNA) has been widely used to study genetic relationships between contemporary Amerindian groups and to infer ancestral migration movements; however inferences about migration routes of prehispanic extinct groups are difficult. Admixture of Neoamerican groups has been characterized by unions between European males and Amerindian females. This allows the identification in present populations of Amerindian mitocondrial haplogroups which give information on ancestral groups. In order to investigate female lineages present in western Venezuela, RFLP haplogroups from mtDNA were obtained from 193 individuals with grandparents from this region, 81 from the State of Lara (Barquisimeto) and 112 from 3 towns of the State of Falcon (Macuquita=25; Macanilla=29 and Churuguara=58). Comparison of haplogroup distributions between groups was performed, and admixture estimates based on female lineages were obtained. The distribution of four Amerindian haplogroups was compared with those of other populations from the American Continent. In our four samples Amerindian haplogroups predominate, followed by those of African origin. In the comparison of the mtDNA Amerindian fraction with other populations we find that Macanillas, Lara and Churuguara are similar to South American and Amazonian groups whilst Macuquita is similar to groups from Aruba. Our findings suggest an important genetic diversity in this region, explained by migration routes to and from the south and the Caribean. They also suggest genetic relationship between prehispanic groups from Aruba and those from the Paraguaná peninsula, which have been inferred by archeological evidences. An increase in sample size and analysis of sequences for more precision is recommended.