Lizbeth Salazar-Sánchez

HLA-A, -B, -C, -DQB1, and -DRB1,3,4,5 allele and haplotype frequencies in the Costa Rica Central Valley Population and its relationship to worldwide populations.

The human leukocyte antigen (HLA) system is the most polymorphic in humans. Its allele, genotype, and haplotype frequencies vary significantly among different populations. Molecular typing data on HLA are necessary for the development of stem cell donor registries, cord blood banks, HLA-disease association studies, and anthropology studies. The Costa Rica Central Valley Population (CCVP) is the major population in this country. No previous study has characterized HLA frequencies in this population. Allele group and haplotype frequencies of HLA genes in the CCVP were determined by means of molecular typing in a sample of 130 unrelated blood donors from one of the countrys major hospitals. A comparison between these frequencies and those of 126 populations worldwide was also carried out. A minimum variance dendrogram based on squared Euclidean distances was constructed to assess the relationship between the CCVP sample and populations from all over the world. Allele group and haplotype frequencies observed in this study are consistent with a profile of a dynamic and diverse population, with a hybrid ethnic origin, predominantly Caucasian-Amerindian. Results showed that populations genetically closest to the CCVP are a Mestizo urban population from Venezuela, and another one from Guadalajara, Mexico.

Novel genotype of Ehrlichia canis detected in samples of human blood bank donors in Costa Rica

This study focuses on the detection and identification of DNA and antibodies to Ehrlichia spp. in samples of blood bank donors in Costa Rica using molecular and serological techniques. Presence of Ehrlichia canis was determined in 10 (3.6%) out of 280 blood samples using polymerase chain reaction (PCR) targeting the ehrlichial dsb conserved gene. Analysis of the ehrlichial trp36 polymorphic gene in these 10 samples revealed substantial polymorphism among the E. canis genotypes, including divergent tandem repeat sequences. Nucleotide sequences of dsb and trp36 amplicons revealed a novel genotype of E. canis in blood bank donors from Costa Rica. Indirect immunofluorescence assay (IFA) detected antibodies in 35 (35%) of 100 serum samples evaluated. Thirty samples showed low endpoint titers (64-256) to E. canis, whereas five sera yielded high endpoint titers (1024-8192); these five samples were also E. canis-PCR positive. These findings represent the first report of the presence of E. canis in humans in Central America.

The frequency of HLA-B(∗)57:01 and the risk of abacavir hypersensitivity reactions in the majority population of Costa Rica.

HLA-B(∗)57:01 is a well-known and cost-effective pharmacogenetic marker for abacavir hypersensitivity. As with other HLA alleles, there is widespread variation in its frequency across populations. The Costa Rica Central Valley Population (CCVP) is the major population in this country. The frequency of HLA-B(∗)57:01 in this population has not been described yet. Thus, our aim was to determine the frequency of this allele in the CCVP. 200 unrelated healthy volunteer donors born in the CCVP were typed. HLA-B(∗)57-positive samples identified by HLA intermediate resolution typing methods were further typed by SBT to high resolution. An HLA-B(∗)57:01 carrier frequency of 5.00% was determined in this sample. This frequency is relatively high in comparison to reports from other populations in Latin America. These results suggest that there is a considerable frequency of HLA-B(∗)57:01 in the CCVP and that pharmacogenetic testing for HIV+ patients who are going to receive abacavir-based treatment should be considered in this country.

Non-therapeutic anti-Xa levels in medical patients receiving anticoagulant therapy with enoxaparin

INTRODUCTION Anticoagulant activity of enoxaparin is not routinely monitored even when previous studies have shown a high pharmacological variability. The aim of this study is to determine the prevalence of non-therapeutic anti-Xa levels among medical patients using enoxaparin as anticoagulant therapy and to point out potential risk factors related to the risk of having a sub-therapeutic level. MATERIALS AND METHODS Anti-Xa levels were measured in a cohort of sixty patients with medical indication for enoxaparin. Patients were categorized according to anti-Xa levels as follows: suboptimal anticoagulation (<0.5 IU/ml), optimal anticoagulation (between 0.5 and 1.2 IU/ml) or overanticoagulated (>1.2 IU/ml). Demographic and clinical variables and the use of concomitant medications were described for each group. Univariate and multivariate analysis were performed to assess the relationship between sub-optimal anticoagulation and potential predictive variables. A linear regression analysis was done to assess the relationship between anti-Xa activity, age, weight, body mass index, administered dose/weight and creatinine clearance. RESULTS The mean anti-Xa activity was 0.71±0.32 UI/ml. Thirty one percent of patients had anti-Xa levels out of the therapeutic range, most of them (twenty-eight percent of total population) with a sub-therapeutic level. None of the variables were associated with the risk of a sub-therapeutic anti-Xa level. CONCLUSION Almost one third of patients receiving enoxaparin had anti-Xa levels out of the therapeutic range. We need more studies to determine the clinical relevance of these findings.

High-resolution HLA allele and haplotype frequencies in majority and minority populations of Costa Rica and Nicaragua: Differential admixture proportions in neighboring countries

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high‐resolution HLA‐A, ‐B, ‐C, and ‐DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub‐Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub‐Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro‐descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high‐resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.

Prevalence of the fibrinogen β‐chain, angiotensin‐converting enzyme and plasminogen activator inhibitor‐1 polymorphisms in Costa Rican young adults with thrombotic disease

Thrombotic disease is a multifactorial condition that involves both classical and genetic risk factors. We studied the association between the classical risk factors of hypertension and smoking, and polymorphisms on the genes of the angiotensin‐converting enzyme (ACE), the β‐chain of fibrinogen (FG), and the plasminogen activator inhibitor‐1 (PAI‐1) in patients with venous and arterial thrombosis. The present investigation is a retrospective case–control study. A total of 340 participants were analyzed, including 162 patients and 178 healthy controls. Hypertension and smoking showed a significant association with thrombotic disease (p < 0.05) but FG level was found significant risk factor only for the venous thrombosis (VT) group (p < 0.04). Significant differences between thrombotic groups were found for the studied polymorphisms of PAI‐1 (p < 0.0014), but for both FG β‐chain gene polymorphisms, none of the molecular analyses showed a positive sample for any mutating allele (p > 0.05). For the ACE polymorphism, the I allele present a protective effect in the general thrombotic group. This is one of the first reports in a Latin‐American population dealing with these molecular markers and thrombotic diseases. Copyright