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Introduction: Host genetics is recognized as an influential factor for the development of dengue disease., Objective: This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN., Materials and Methods: Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry., Results: For Afro-Colombians, the allele rs8192284 C offered protection against dengue [OR=0.425,(0.204-0.887), p=0.020]. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians [OR=2.389, (1.170-4.879), p=0.015] and Mestizos [OR=2.329, (1.283-4.226), p=0.005]. The reproducibility for rs8192284 C/C [OR=2.45, (1.05-5.76), p=0.013] remained after adjustment by Amerindian ancestry [OR=2.52, (1.04-6.09), p=0.013]. The reproducibility for rs3775290 A/A [OR=2.48, (1.09-5.65), p=0.033] remained after adjustment by European [OR=2.34, (1.02-5.35), p=0.048], Amerindian [OR=2.49, (1.09-5.66), p=0.035], and African ancestry [OR=2.37, (1.04-5.41), p=0.046]. Finally, the association of dengue fever with the allelic combination CAG [OR=2.07, (1.06-4.05), p=0.033] remained after adjustment by Amerindian ancestry [OR=2.16, (1.09-4.28), p=0.028]., Conclusions: Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population.

Introduction: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines., Objective: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population., Materials and Methods: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chi-square and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component., Results: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components., Conclusions: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.

Introduction: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied., Objective: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection., Materials and Methods: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant., Results: Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006)., Conclusion: Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

Introduction: Mitochondrial DNA has proven its utility for the study of insect evolution. Genes such as cytochrome b (Cytb) and the transfer gene for serine (SertRNA) can be used to compare closely related organisms., Objective: The phylogenetic utility of Cytb-SertRNA-IG1-ND1 was tested for polymorphisms, and secondary structure modeling in SertRNA was done to detect possible cryptic species in Anopheles neivai., Materials and Methods: Specimens from Colombia, Guatemala, and the type locality in Panamá were collected and sequenced for specimen comparison based on DNA polymorphisms, and secondary structure modeling for the SertRNA gene., Results: Thirty-six sequences for A. neivai and A. pholidotus were obtained., Conclusions: Polymorphic variants were detected in A. neivai for Cytb-SertRNA-IG1- ND1. Despite this variation in A. neivai, cryptic species could not be detected.

Introduction: Aedes aegypti populations may experience changes in abundance and genetic diversity in addition to changes in their evolutionary capability to respond to vector control. The knowledge on the changes in genetic variation on a spatio-temporal scale improves the epidemiological understanding of dengue and supports the appropriate and timely design of vector control strategies., Objective: To assess the genetic changes, diversity and gene flow in six microgeographical populations of Ae. aegypti in Medellín for different epidemiological periods of dengue., Materials and Methods: A total of 255 specimens from six different neighborhoods in Medellín were used to assess variations in the CO1 mtDNA haplotype composition, diversity and genetic differentiation for an epidemic period (2010) and an endemic period (2012)., Results: Two groups of highly differentiated haplotypes were present in both periods, and a high-frequency haplotype was assessed for all neighborhoods. The highest haplotype diversity was recorded in 2012, but the maximum nucleotide diversity was recorded in 2010. No significant correlation between genetic and geographic distances was observed., Conclusions: The genetic composition of Ae. aegypti varies over time without a predictable pattern. In addition, the presence of a high-frequency haplotype in both periods could indicate a persistent variation adapted to vector control. However, the simultaneous movement of highly differentiated CO1 haplotypes compatible with multiple introductions suggests that different gene pools would be suitable for transmission. These results are consistent with mosquito dispersion due to human activities, which would enable the rapid spread of the virus during epidemics in Medellin.

Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations., Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia., Methods and Materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined., Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure., Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

Introduction: Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations., Objectives: The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia., Materials and Methods: In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods., Results: A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001)., Conclusion: Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Introduction: The environmental risk factors such as food intake and physival activity, are determinants in the etiology of metabolic syndrome in overweight adolescents., Objective: To explore the association between environmental risk factors and components presence of metabolic syndrome in overweight youngsters in Medellín., Materials and Methods: Adolescents between the ages of 10 and 18 were selected for a cross sectional study. Body composition by anthropometry, blood pressure, lipid profile, glucose, insulin, food intake and physical activity level were assessed in the study population., Results: The prevalence for metabolic syndrome components of hypertriglyceridemia was 40.9%; hypertension, 20.9%; low HDLc, 15.6%; high waist circumference, 4.0%, and hyperglycemia, 0.9%; the overall prevalence of metabolic syndrome was 3.1%. There was a statistical difference (p<0.005) between the consumption of calories, simple and total carbohydrates and the presence of the components; no association was found between the level of physical activity and the presence of components (p>0.05). The logistic regression model showed a higher probability of having at least one component if the youngster was male (p=0.022), with a higher BMI (Body Mass Index)(p=0.019) and was located in the fourth simple carbohydrates consumption quartile (p=0.036)., Conclusions: Environmental risk factors associated with components of metabolic syndrome were the increased consumption of calories, simple and complex carbohydrates, all directly related to the BMI. In contrast, the level of physical activity, family history and personal risk factors showed no association. The metabolic syndrome only occurred in youngsters with obesity.

Introduction: The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance., Objective: The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus., Materials and Methods: In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry., Results: Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p = 0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found. These associations remained after adjustment using individual genetic admixture estimates., Conclusion: Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.

Introduction: The E280A mutation of the presenilin 1 gene has been found to be the most common associate in Alzheimers patients with a family history of this disease. Presenilin 1 is a critical component of the g-secretase complex and plays an essential role in the production of amyloid-beta peptide. This peptide has been strongly associated with the physiopathology of the disease., Objective: The E280A mutation in the presenilin 1 was investigated for increased production of amyloid-beta , as a response to gain in gamma-secretase function., Materials and Methods: Levels of systemic amyloid-beta were measured with congo red staining and immuno-histochemistry of the tissues of affected cadavers, compared with non-affected cadavers. The 40 and 42 amino acid amyloid-beta levels were quantified by ELISA assay in CHO cell cultures. The amyloid precursor protein expressed by the cultures was detected by transfection with the cDNAs of presenilin 1 carrying the M146L, E280A, DE9 y L392V mutations., Results: Protein deposits were found in all tissues investigatged, but only a few with beta -amyloid deposition. No differences were observed in the amount or location of amyloid-beta between affected and unaffected cadavers. Not increase was noted in the production of amyloid-beta from the CHO cells transfected with cDNA from any of the mutations of presenilin 1., Conclusions: The E280A mutation in the presenilin 1 gene was not associated with the increased production of amyloid-beta in non-neuronal peripheral tissues, or in the in vitro model. This is in contrast to the expectation in a gamma-secretase gain of function.

Introduction: Genetic studies of Trypanosoma cruzi have tried to establish relations between genetic variants and their biological characteristics, such as clinical manifestations, host or geographic origin. However, much controversy exists on the associations between the commonly used DNA markers with group, clinical characteristics and disease epidemiology., Objective: In this study determined the variability of the genes that code for the proteins trypanothione reductase and cruzipain, both involved in the infection and survival of the parasite in the mammalian host, was studied and the association between genetic polymorphism and biological and geographic sources in Colombian T. cruzi strains was examined., Materials and Methods: The genotypes for each of six SNPs (single nucleotide polymorphisms) for trypanothione reductase and eight SNPs for cruzipain genes were identified by polymerase chain reaction-restriction fragment length polymorphism in 36 T. cruzi Colombian stocks from several regions and biological origins., Results: Three genotypes were identified for trypanothione reductase with Acy I and Hae III enzymes and six genotypes for cruzipain with the Rsa I, Ban I and Bsu 361 enzymes., Conclusions: For trypanothione reductase, an association was not established with biological or geographical origin; however, alleles at positions 102 and 210 allowed discrimination with groups I and II. For cruzipain, specific genotypes were associated with group, biological and geographic origin. The usefulness of molecular markers on these genes was demonstrated for the determination and differentiation of genetic varieties in T. cruzi.

Introduction: Surname frequency (isonymy) is used as a marker of paternal lineage and is used to characterize human population structure. Principles of isonymy were used to determine the genetic structure, migration rates, ancestry relations and origins of populations. This analysis was applied to two historically related local populations which currently are considered to be genetically isolated., Objective: The genetic relationships and influence zones of the Aranzazu and Marinilla populations were assessed by means of surname frequency analysis., Materials and Methods: Data originated from database with the title "System of Identification of Beneficiaries of the Social Programs" database or Sisben. Population parameters such as a priori kinship (phi(ii)), population homogeneity with B and C estimators, and Cavalli-Sforza's genetic distance were calculated for (a) three towns of Marinilla and its influence zone and (b) Aranzazu. The Rionegro population served as an external, comparison population., Results: The Aranzazu and Marinilla populations showed the higher homogeneity (B value between 0.25 and 0.5) in contrast with Rionegro (B = 0.159), as well as greater a priori kinship values (4), between 0.003 and 0.010). The lowest distances were found between Marinilla and Aranzazu., Conclusions: Aranzazu is a population with characteristics similar to those of Marinilla and its influence zone. The close similarity of genetic characteristics for these populations is due probably to a founder effect. Furthermore, the genetic similarity predicts that genetic diseases will have the same etiology in both populations and provides optimum conditions for gene mapping studies.

An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was translated into Spanish for application in studies of psychiatric disorders in Colombia. Two Spanish translations of the original English version of DIGS were prepared and back-translated into English. A review committee verified the linguistic and cultural equivalence of the translations. The evaluator and test-retest reliability were assessed calculating Cohen's kappa for samples of 65 and 91 patients respectively. DIGS proved valid in both appearance and content. The confidence interval (C.I.) was excellent for schizophrenia (kappa = 0.81, C.I. 95% = 0.68-0.93), bipolar disorder (kappa = 0.87, C.I. 95% = 0.75-0.99), major depressive disorder (kappa = 0.86, C.I. 95% = 0.70-1.00), and for a normal diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective disorder (kappa = 0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was excellent for all diagnoses (kappa > 0.8), except for "other psychiatric diagnoses" (kappa = 0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the DIGS was comprehensible, with face and content validity, and good test-retest and evaluator reliability. This translation will be a useful tool for genetic studies of psychiatric disorders in Latin America, particularly where schizophrenia and affective disorders are involved.