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CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted.

CYP2D6 differences have already been demonstrated within Latin American populations by the CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics (RIBEF, as per the acronym in Spanish). However, within the population of Costa Rica, no research has been conducted until now, even though this population has a trihybrid component ancestry that represents an interesting condition. Thus, the present study was aimed to determine the frequency of Ultra-rapid Metabolizers (UMs) and Poor Metabolizers (PMs) in a Costa Rican population, as well as to determine whether there are differences in the CYP2D6-predicted phenotype frequencies among three Costa Rican groups with different ethnic backgrounds. Additionally, these frequencies of PMs and UMs obtained were compared with Ibero-American populations published data. Finally, we also aimed to describe allele frequencies among different Costa Rican ethnic groups. This research has been undertaken within the framework of the RIBEF CEIBA Consortium studies on Latin American populations. A total of 385 individuals were included in the study: 139 mestizos, 197 Amerindians, and 49 Afro-Caribbeans. CYP2D6 genotypes were determined by XL-PCR and Real-Time PCR. The CYP2D6 variant alleles *2, *3, *4, *5, *6, *10, "17, *29, *35 and *41 were also determined. For the entire Costa Rican population, the frequency of PMs and UMs was 6% and 6.5%, respectively. The percentage of UMs in the mestizo population was higher than in the Amerindian population. CYP2D6 UMs vary from 3.6% to 10.1% and PMs from 1.4% to 10.2% among three Costa Rican groups. The highest frequencies of UMs (10.1%) and PMs (10.2%) were found in the mestizo and Amerindian populations, respectively. In conclusion, the frequencies of UMs and PMs for CYP2D6 varied widely across the mestizo, Amerindian and Afro-Caribbean Costa Rican populations. Future research in this population should be oriented to identify new CYP2D6 variants through sequencing methods, as well as to determine CYP2D6 phenotype, in order to establish the phenotype-genotype relation. Finally, further studies involving genetic markers of ancestry are needed in the Costa Rican population.

The STR (AAAAT)n within intron 1 of the TP53 locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans, and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126/7 (bp/copies of the repeat), 131/8 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R(ST)) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within Europeans.

In the last decade, the Costa Rican Central Valley population (CRCV), has received considerable scientific attention, attributed in part to a particularly interesting population structure. Two different and contradictory explanations have emerged: (1) An European-Amerindian-African admixed population, with some regional genetic heterocigosity and moderate degrees of consanguinity, similar to other Latin-American populations. (2) A genetic isolate, with a recent founder effect of European origin, genetically homogeneous, with a high intermarriage rate, and with a high degree of consanguinity. Extensive civil and religious documentation, since the settlement of the current population, allows wide genealogy and isonymy studies useful in the analysis of both hypotheses. This paper reviews temporal and spatial aspects of endogamy and consanguinity in the CRCV as a key to understand population history. The average inbreeding coefficients (a) between 1860 and 1969 show a general decrease within time. The consanguinity in the CRCV population is not homogeneous, and it is related to a variable geographic pattern. Results indicate that the endogamy frequencies are high but in general it was not correlated with a values. The general tendency shows a consanguinity decrease in time, and from rural to urban communities, repeating the tendencies observed in other countries with the same degree of development, and follows the general Western World tendency. Few human areas or communities in the world can be considered true genetic isolates. As shown, during last century, the CRCV population has had consanguinity values that definitively do not match those of true genetic isolates. A clear knowledge of the Costa Rican population genetic structure is needed to explain the origin of genetic diseases and its implications to the health system.

A study of several loci blood groups (ABO, Diego, Duffy, Kell, Kidd, Lewis, Lutheran, MNSs, P, Rhesus and Secretor), and Hp serum protein was carried out on a sample of 2,196 unrelated Costa Rican individuals of both sexes. Data was classified and analyzed according to geographic regions. Gene frequencies and the goodness of fit to Hardy-Weinberg equilibrium were estimated by the maximum likelihood method. A geographic structuring was observed in the Costa Rican population. All the regions of Costa Rica show higher heterozigosity values than the ones observed in the indigenous Costa Rican groups, but similar or slightly higher than the ones observed in the Spanish populations. The genetic distance analysis evidenced that the regions of Costa Rica group close to each other in intermediate positions between the Amerindians and the Spanish, fact that is coherent with the statement that attributes a intermediate origin to the general population of Costa Rica. The data contradicts the idea that the Central region has a radically different population than the rest of the country. The outcome of these markers revealed poor values of exclusion probability in forensic and paternity cases, which confirms the importance of their replacement for DNA markers in the outlines of human identification of judicial investigation systems. These results are similar to other studies made in Latin American populations.

The genetic diversity of nine Amerindian tribes (Boruca, Bokota, Bribrí, Cabecar, Guatuso, Guaymí, Huetar, Kuna and Teribe) from Costa Rica and Panama were analyzed using 48 loci of enzymatic systems, blood groups and serum proteins. The average heterozygosity (H) and the frequency of polymorphisms (P) for this assemblage are relatively low (H = -0.055; P = 0.217). The genetic differentiation within tribes is also low with the exception of the Cabecar (Gst = 0.049). However it is high between tribes (Gst = 0.073). These populations have some racial admixture and negro and caucasian genes are present in different frequencies (1-30%) depending on their ecological and cultural background. Mating systems and random genetic drift should explain these results. In a broad sense the genetic diversity of these Chibchan tribes are similar to others from South America which use different languages.

A screening of more than 40 loci was performed in the Bribri and Cabecar Amerindian populations of Talamanca in Southeastern Costa Rica. Some differences were found in the distribution (presence or absence) of the variants (some of them private) of the GOT, PEPA, RH, TF and TPI loci when the results reported here were compared with those of the Bribris and Cabecars that inhabit in the Pacific side of the country. Admixture with non-Indians was detected at the ABO, ADA, and G6PD loci. The proportion of polymorphic loci (P) found were 17.1 in the Bribris and 19.4 in the Cabecars; their average heterozygosites (H) estimates were 0.039 and 0.049 respectively. Fst values (0.019 in the Bribris and 0.056 in the Cabecars) seem to indicate that random events have played important roles in the divergence of the Cabecars. Low effective population sizes of the emigrant groups to the Pacific side and probable gene flow in the case of the Bribris, could be the cause of these differences.

Digital and palmar dermatoglyphic patterns were analysed for 286 male and female Bribri and Cabecar Amerindians of Chibcha ascendancy from four populations located in southeastern Costa Rica. There was no significant difference among Pacific and Atlantic Cabecar samples, with the exception of the bc and cd ridge count. However, the Bribri groups present differences for 22 features, though the largest differences are between Bribri and Cabecar Pacific populations. A comparison with other Latin-American indians evidence that dermatoglyphic patterns of Bribri and Cabecar tribes are within the expected range, but it is important to notice the high frequency of digital arcs and the low frequency of worls. The results are similar to those observed using other genetic markers in the same populations, and demonstrate the discriminable capacity of the dermatoglyphics to tribal level for taxonomic and evolutionary studies.

Diego blood group was studied in 141 Amerindian and Eskimo tribes from Alaska and Canada. Twenty six tribes (18%) did not show the Di-a antigen and 20 tribes (77%) were of the Chibcha linguistic Phyla. In the past, the Di-a absence has been related to several ecological factors such as climate and the presence of clines. I advance an alternative explanation regarding the loss of the Di-a allele in the Chibcha genetic divergence which occurred 6000-7000 years ago, as a consequence of random processes and not of natural selection. It is postulated that the Di-a allele is absent in this Amerindian groups only, and that the presence of the antigen in four tribes (Boruca, Ica, Kuna and Sumo) is due to gene flow across neighboring groups of different languages which carry the Di-a antigen.

Genetic structure of the population of Matambú, Costa Rica, was investigated using 6 genetic markers: ABO and Rh blood groups, and 4 serum proteins: albumin, ceruloplasmin, haptoglobin and transferrin. All the individuals were Rh+ and the I degrees allele had a high frequency (0.89). There are 4 polymorphic alleles in ceruloplasmin, including a possible new variant (3.8%). Transferrin Dchi had a remarkably high frequency (0.11). These results indicate that this group is of Amerindian origin although there are Caucasic and Negroid genes present. The genetic constitution of Matambú differs from that of the other Amerindian groups such as the Guaymí, from Chibcha stock, which supports the hypothesis of a Mesoamerican origin.

Some anthropological and genetic features of the Guaymi Amerindian group of Costa Rica and Panama are described in an ecological context. The fission-fusion phenomenon and the lineal effect are present; however, there are some important differences in relation to other hunter gatherer indian groups. These adaptation patterns are important for the genetic structure and evolution of the Guaymi Amerindians in the Intermediate Zone.

A demographic and genetic study of the Guaymi Amerindian population at limoncito, Coto Brus, Costa Rica, showed that 47% of the population is between the ages of 0 and 14 and 35% between 15 and 44. The sex ratio is 91, which is evidence of a greater number of females. Forty percent of the couples come from Panama, but the filial generation (98%) was born in Limoncito. Emigration is very low. The selective potential is relatively high (0.94), with the mortality component predominating. Endogamy and the inbreeding coefficient have high values and polyginy is common. The effective and reproductive size of the population is small. Evolutionary implications of the results are discussed.

An analysis of 1315 cases of gastric cancer from the records of the Ministry of Public Health, San José, Costa Rica between 1977 and 1980 showed important geographical differences in the incidence, and especially in relation to the sex ratio, age structure and migratory patterns. Rates of incidence ranged between 12.6 and 153.2 per 100,000 inhabitants in men and 10.6 and 56.6 in women. Variations in the incidence of gastric cancer rates were studied in relation to ecological parameters, including certain soil and drinking water characteristics as well as the presence of vitamins A and C in serum. No significant relation was found between gastric cancer rates and the presence of vitamins and of several components in drinking water. However, a multivariate analysis considering nine soil components and pH showed a statistically significant (p less than 0.01) association with pH, K, Zn and Fe, which account for 22% of the variation in the incidence rates. A dynamic and multifactorial model is proposed to explain regional variations in cancer rates, with a tentative application of this model to the results obtained.

A study of consanguinity and population structure was carried out in a sample of 498 consanguineous (MC) and 570 non-consanguineous matings (MNC) in the Parrish of Dota, Costa Rica, during a period of 75 years. The inbreeding coefficient (F) shows fluctuations in time (476 to 194 x 10(-5) with an increase from 1888 to 1917, followed by a decrease in the last years but remains high in nonmigrant marriages. There is a high frequency of unions among second cousins. The endogamy percentage is high, greater in MC (80%) than in MNC (61%). Exogamy tends to diminish with time among both types of union. Effects of age distributions in the groups was not found. Marital and migrational distances are short and tend to become shorter in the final periods. There is a positive correlation (r = 0.71; p less than 0.05) between these distances in MC but not in MNC; distances are shorter in MC. Immigration is minimal and reduced to short distances. Post-marital movement is intense (37%) and involves greater distances. Emigratory behavior is identical in MC and MNC.