Publications by authors named "Lisbeth Borjas"

14 Publications

  • Page 1 of 1

[Study of the association between the polymorphism of the TNF-α gene and prostate cáncer].

Rev Alerg Mex 2019 Apr-Jun;66(2):154-162

Universidad del Zulia, Facultad de Medicina, Instituto de Investigaciones Genéticas, Maracaibo, Venezuela.

Background: Prostate cancer is the third cause of cancer death in men in the Western hemisphere and the second cause of cancer death in Zulian men from Venezuela.

Objective: To determine whether polymorphisms 308 and 238 of the tumor necrosis factor alpha (TNF-α) gene are associated with prostate cancer.

Methods: The DNA that was extracted from the peripheral blood of 40 patients with prostatic specific antigen and 40 controls was amplified by PCR plus digestion with enzymes NcoI and MspI.

Results: In the patients, genotypes of the TNF-α-238 polymorphism were observed in 90% GG and 10% GA; in controls, in 97.5% GG and 2.5% GA, odds ratio (OR) = 4,000 for GA. In the patients, genotypes of TNF-α-308 polymorphism were identified in 85% GG and 15% GA, and in controls in 72.5% GG and 27.5% GA, OR = 0.545 for GA and 1.172 for GG. The allelic frequencies for TNF-α-238 in patients were 95% for G and 5% for A; in controls, 98.75% for G and 1.25% for A, with OR = 4,000 for A. The allelic frequencies for TNF-α-308 in the patients were 92.5% for G and 7.5% for A.

Conclusions: There weren't any statistically significant associations. The allele A of the TNF-α-238 polymorphism resulted in a considerable risk factor for prostate cancer.
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http://dx.doi.org/10.29262/ram.v66i2.517DOI Listing
January 2020

Distribution of GSTM1, GSTT1, GSTP1 and TP53 disease-associated gene variants in native and urban Venezuelan populations.

Gene 2013 Nov 27;531(1):106-11. Epub 2013 Aug 27.

Laboratorio de Genetica Molecular, Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela. Electronic address:

The contemporary Venezuelan population is the product of major admixture process across various historical events, which has provided it a particular genetic background. The aim of this study concerns the analysis of glutathione S-transferase (GST) GSTM1, GSTP1 and GSTT1 genetic variants and five polymorphisms at the TP53 gene, which are related to cancer susceptibility, in an urban/admixed population and five Amerindian tribes (Bari, Panare, Pemon, Warao and Wayuu) from Venezuela. Genotyping was carried out in 120 individuals from an urban sample and 188 Amerindians. The analysis performed on TP53 haplotype and GST allele distribution showed a close correlation for Pemon and Warao populations, while Bari group appears isolated from the other populations. GSTT1 null variant frequency in our admixed (11%) and native samples (0.0-11.4%) was lower when compared with Caucasians, Africans and Asians. Frequency of the GSTP1*Val cancer-associated allele found in Bari (88.6%) and Panare (63.0%) is of the highest so far reported. Fourteen TP53 haplotypes were observed in the admixed populations, whereas only 3 to 5 in Amerindians. To our knowledge this is the first report of GST polymorphisms and TP53 haplotype distribution in Venezuelans. The distribution of most of analyzed polymorphisms in the urban sample is consistent with the admixed origin of the present-day population of Venezuela. While, the inter-ethnic variations in genetic polymorphisms found in Native American tribes seem to be the result of the influence of demographic factors. These results provide additional data for undertaking ethnographic and disease association studies in Venezuela.
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http://dx.doi.org/10.1016/j.gene.2013.08.055DOI Listing
November 2013

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome.

Int J Pediatr Endocrinol 2013 Jun 4;2013(1):10. Epub 2013 Jun 4.

Unidad de Endocrinología Pediátrica, Hospital de Clínicas Caracas, Caracas, Venezuela.

Background: It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients.

Methods: This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n =  93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n =  34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined.

Results: Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm.

Conclusions: The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.
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http://dx.doi.org/10.1186/1687-9856-2013-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679778PMC
June 2013

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans.

PLoS Genet 2013 Apr 11;9(4):e1003460. Epub 2013 Apr 11.

Institute of Legal Medicine and Forensic Sciences, Department of Forensic Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans.
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http://dx.doi.org/10.1371/journal.pgen.1003460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623769PMC
April 2013

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

PLoS Genet 2012 8;8(3):e1002554. Epub 2012 Mar 8.

University of California San Francisco, San Francisco, California, United States of America.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.
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http://dx.doi.org/10.1371/journal.pgen.1002554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297575PMC
September 2012

CYP2D6 gene variants in urban/admixed and Amerindian populations of Venezuela: pharmacogenetics and anthropological implications.

Ann Hum Biol 2012 Mar;39(2):137-42

Laboratorio de Genética Molecular Dr Jorge Yunis-Turbay, Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela.

Background: Differences in genes encoding enzymes involved in the biotransformation of a large number of compounds, such as CYP2D6, are related to inter-individual and inter-ethnic variability in the metabolism of many drugs, which have also been linked to susceptibility to cancer and other health outcomes. Therefore, populations are likely to benefit from inclusion in pharmacogenetic research studies.

Aim: To determine the frequency of functionally important allele variants of CYP2D6 gene in a sample of an Urban/admixed and five Amerindian Venezuelan populations.

Subjects And Methods: DNA of 328 unrelated volunteers was analysed for the presence of CYP2D6 *2, *3, *4, *5, *6 and *10 variants.

Results: The frequency in the Urban/admixed population for *2, *3, *4, *5, *6 and *10 alleles was 37.9%, 0%, 13.4%, 2.0%, 1.2% and 4.0%, respectively. In the Bari population, the prevalence of *4 allele associated with decreased enzyme activity was observed in 42.5%, whereas the poor metabolizer genotype *4/*4 was found in 25%. In the Panare, Pemon, Warao and Wayuu populations the *4 allele was found in 5.4%, 2.5%, 1.7% and 4.2%, respectively. The *10 allele frequency found in Amerindians (0.0-6.3%) was lower than reported for Asians.

Conclusion: The results are consistent with the known genetic admixture origin of most Venezuela populations. Nevertheless, the observed significant differences among Amerindians highlight the need for pharmacogenetic studies taking into account biogeographical and anthropological considerations.
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http://dx.doi.org/10.3109/03014460.2012.656703DOI Listing
March 2012

[Intragenic polymorphisms of factor VIII and IX genes and their utility in the indirect diagnosis of carriers of Haemophilias A and B].

Invest Clin 2010 Sep;51(3):391-401

Laboratorio de Genética Molecular, Unidad de Genética, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venzuela.

Haemophilia A and B are considered sex-linked inherited diseases caused by mutations in genes that encode factors VIII and IX, respectively. This results in the deficiency of these proteins plasma levels which are actively involved in the mechanism of blood coagulation. It has been reported that several mutations are responsible for the alteration of these genes, which is why the application of a molecular diagnostic method for the direct identification of female carriers is impractical. An appropriate diagnostic strategy is the indirect analysis of polymorphisms linked to the gene. The aim of this study was to identify female carriers in different families with history of HA and HB that live in Zulia State, Venezuela, characterizing intragenic gene polymorphisms of the clotting factors VIII and IX, which helped to identify and assign haplotypes, to diagnose or to exclude the carrying condition, to 95% of women who were needing the study for HA and to 100% for HB.
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September 2010

Novel mutations identification in exon 4 of LDLR gene in patients with moderate hypercholesterolemia in a Venezuelan population.

Am J Ther 2010 May-Jun;17(3):325-9

Endocrine and Metabolic Diseases Research Center, University of Zulia, Maracaibo, Venezuela.

Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by increase in low-density lipoprotein (LDL) cholesterol levels and premature coronary artery disease. In Venezuela, the molecular basis of FH has not been characterized, thus, the aim of this study was to investigate mutations in the exon 4 of the LDLR (LDL-receptor) gene in 225 Venezuelan mixed race individuals (65 hypercholesterolemic and 160 normolipidemic). The exon 4 of the LDLR gene was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Additionally, ApoB-100 gene mutations were investigated. Different LDLR gene mutations were identified in 5 hypercholesterolemic patients (7.7%), 3 missense mutations (4.6%), and 2 frameshift mutations (3%). All mutations were heterozygous. The missense mutations included the amino acid substitution p.E180K, p.R194S, and p.C152G. The frameshift mutations are caused by insertions resulting in the creation of stop codons: p.D157fsX158 and p.S173fsX174, which could code for truncated LDLR of 157 and 173 amino acids, respectively. The apoB gene mutations were not detected in any of our patients and to our knowledge 4 mutations identified in this study have not been reported previously, this study being the first comprehensive mutation analysis of the LDLR causing FH in our region. The early identification of individuals at risk allows changes in lifestyle, including dietary intervention, followed by drug treatment.
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http://dx.doi.org/10.1097/MJT.0b013e3181c1234dDOI Listing
August 2010

[G138A polymorphism of the RNASEL gene and its association with the development of prostate cancer. Preliminary study].

Invest Clin 2009 Sep;50(3):295-301

Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

Prostate Cancer (CAP), is a complex disease with a multifactorial origin. It is characterized by heterogenous patterns of growth of neoplasic tissue, varying widely in its progression, age of beginning and therapy response. It is considered as the second most common cause of death by cancer in men and, it has been estimated, that one of five, suffers of CAP through the course of his life. The genetic etiology of neoplasic transformation of normal prostate cells is still not known; nevertheless, investigations in epidemiology have demonstrated a strong genetic component in its development, suggesting so much a pattern of mendelian inheritance as the presence of loci of susceptibility throughout the human genome. It has been described a cromosomic location related to the CAP in locus 1q24-25, denominated HPC1, where the gene RNASEL is located, and the seggregation of its alleles has been associated with the development of CAP in numerous familiar groups. The RNASEL gene codifies for a ribonuclease protein that degrades vi-ral and cellular ARN and takes part in the apoptosis. A decrease of the enzymatic activity up to three times in carriers of the G1385A polymorphism of this gene has been reported, and the same has been associated frequently with the development of CAP. Using a variant of the Polymerase Chain Reaction, Allele specific amplification, this investigation had as objective to determine the association between variant G1385A and CAP, in a sample of 103 masculine individuals with and without CAP, pertaining to the population of Maracaibo, Venezuela. An association between these variants and CAP could not be demonstrated.
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September 2009

[Frequency and clinicopathological associations of K-ras mutations in Venezuelan patients with colo-rectal cancer].

Invest Clin 2009 Mar;50(1):55-63

Universidad Centro Occidental Lisandro Alvarado, Barquisimeto, Venezuela.

Mutations in the K-ras oncogene are common in colo-rectal cancer, which affect the biological behaviour and may influence the susceptibility to therapy in these tumors. The objective of this work was to identify the types of K-ras mutations observed in referred patients with colo-rectal cancer and to relate them to their degree of histological differentiation and clinical stage. Histopathological and clinical data were obtained from medical records. DNA was obtained from both, fresh tissue and tumor tissue embedded in paraffin. The K-ras gene was amplified through the polymerase chain reaction (PCR) and the amplified fragments were digested with restriction enzymes. We found mutations in codons 12 and 13 of the K-ras oncogene in 23.33% of patients. Of these, 28.57% were located at codon 12, 57.14% were at codon 13 and 14.29% at both codons. They were more frequent in tumors located in the left hemicolon and, according to their histological type, were more frequent in well differentiated adenocarcinomas (58.70%) and in mucinous (28.57%). The identified mutations were more frequent in advanced stages (C2) of Dukes' classification. The molecular analysis of the K-ras oncogene made mutations evident, which could be useful in the diagnosis and prognosis of colorectal tumors. The frequency of mutations found in this work is similar to some of those reported worldwide; however, they differ in the more frequent type of mutation, which, in our study, was located at codon 13 in more than 50% of the cases.
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March 2009

[Association of the vitamin D receptor gene BBAAtt haplotype with osteoporosis in post-menopausic women].

Invest Clin 2008 Mar;49(1):29-38

Cátedra de Bioquímica Clínica, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

Osteoporosis (OP) is an important public issue affecting more than 150 millions all over the world, mainly post-menopausic women. Epidemiological studies have shown that the genetic factors could be involved in 80-90% of the bone mineral density variabiblity and therefore, related to the risk of OP manifestations. The vitamin D receptor (VRD) gene has been extensively studied, but its relationship with OP has been controversial. The aim of this investigation was to study the association of Bsm I, Apa I and Taq I VDR gene polymorphism with OP in 147 post-menopausic women; 71 with OP and 76 without the disease (control). The molecular gene analysis was performed using the polymerase chain reaction (PCR). The genotypes BB, AA, and tt were found in 56.33, 50.70 and 25.35% and in 21.05, 28.95 and 10.53% of OP patients and controls respectively. The haplotype BBAAtt was observed in 23.94% of OP patients and 5.26% of the controls. This haplotype was a risk factor for OP, since a odds ratio (OR) of 5.66 was found, while, haplotype BbaaTT was a protection factor (OR: 0.10). These findings support the association of the vitamin D receptor gene BBAAtt haplotype with OP.
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March 2008

Usefulness of 12 Y-STRs for forensic genetics evaluation in two populations from Venezuela.

Leg Med (Tokyo) 2008 Mar 5;10(2):107-12. Epub 2007 Nov 5.

Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

The distribution of allele frequencies and haplotypes for 12 STRs loci, (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438 and DYS439) on the Y-chromosome from two Venezuelan populations were determined in 173 DNA samples of unrelated males living in Caracas (62) and Maracaibo (111). Some parameters of forensic importance were calculated. AMOVA and genetic distances between these populations were estimated. The results confirmed Y-STR genotypes as useful markers for forensic genetics analysis.
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http://dx.doi.org/10.1016/j.legalmed.2007.08.005DOI Listing
March 2008

Genetic variation of 15 STR autosomal loci in the Maracaibo population from Venezuela.

Forensic Sci Int 2006 Aug 6;161(1):60-3. Epub 2005 Sep 6.

Laboratorio de Genética Molecular, Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Maracaibo 4007, Venezuela.

Allele frequencies for 15 short tandem repeats (STRs) autosomal loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA, included in the AmpFLSTR Identifiler, Applied Biosystems) were studied in the city of Maracaibo, Venezuela and were compared with other published Latin-American populations for the same loci. Population and forensic parameters were estimated.
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http://dx.doi.org/10.1016/j.forsciint.2005.07.011DOI Listing
August 2006

Del(1)(q23) in a patient with Hutchinson-Gilford progeria.

Am J Med Genet 2002 Dec;113(3):298-301

Unidad de Genética Médica, Facultad de Medicina de La Universidad del Zulia, Maracaibo, Venezuela.

A 9-year-old patient with the classical clinical picture of Hutchinson-Gilford progeria (HGP) is described. The karyotype shows a 46,XY,del(1)(q23) constitution. Our findings suggest that the interval 1q23 may play a roll in the etiology of HGP. A perturbation in glycosylation in connective tissue has been demonstrated in patients with this condition. This abnormality may be due to a defect in the UDP-galactose:beta-N-acetylglucosamina-beta-1,4-galactosyltransferase 3 (B4GALT3) gene that has been mapped in the interval 1q21-23. The cytogenetical analyses of this patient suggest that the B4GALT3 gene could be involved in the pathogenesis of HGP.
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http://dx.doi.org/10.1002/ajmg.10753DOI Listing
December 2002