The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be populationdependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n =256) and 257 age and sex groupmatched controls from a random sample of free living Colombians (n =2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equi-

These findings show a positive association between the MSX1 CA polymorphism and CL+/-P in a Colombian group population.

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg +/- 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (XPA through XPG and XPV). The XP-V (variant) subtype of the disease results from mutations in a gene (XPV, also named POLH) which encodes for Polη, a member of the Y-DNA polymerase family. Although the presence and severity of skin and neurological dysfunctions differ between XP subtypes, there are overlapping clinical features among subtypes such that the sub-type cannot be deduced from the clinical features.In this study, in order to overcome this drawback, we undertook whole-exome sequencing in two XP sibs and their father. We identified a novel homozygous nonsense mutation (c.897T>G, p.Y299X) in POLH which causes the disease. Our results demonstrate that next generation sequencing is a powerful approach to rapid determination of XP genetic etiology.

No abstract

Introduction: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected. Materials and Methods: A case-control study exploratory was carried out in a cohort of infected patients. 540 individuals were selected in total, 270 patients with sepsis and 270 controls (infected but non-septic), classified according to the 2016 consensus (Sepsis-3). The presence of the single-nucleotide polymorphism (SNP; allele T and/or allele C) was determined through analyses of restriction fragment length polymorphism and plasma levels of MMP-9 were determined through enzyme-linked immunosorbent assay immunoassay. Results: SNP MMP-9 -1562 has two known alleles (T and C), with predominance of the C over the T allele; in the group of patients with sepsis, T allele was found in 7.2% of cases, while C allele in the rest (92.8%); in comparison, in the group of infected but non-septic patients, frequencies were 9.4% for T allele and 90.6% for the C allele ( P = .33). Also, the presence of the polymorphic T allele was not related to the levels of MMP-9 in patients with sepsis in comparison with infected but non-septic patients 780 (397-1375) ng/mL vs 646 (172-1249) ng/mL ( P = .64). There was also no association between the SNP and sepsis mortality ( P = .78). Conclusions: We concluded that there was no association between the SNP MMP9 -1562 C/T and sepsis or between the SNP MMP9 -1562 C/T and sepsis mortality in the Northeastern Colombian septic patient cohort. Further research is needed to clarify the correlation among sepsis, genetic factors with allele T and MMP-9 plasma concentration.

61Genética del cáncer de mama ARTÍCULO ORIGINAL Análisis de las mutaciones más frecuentes del gen BRCA1 (185delAG y 5382insC) en mujeres con cáncer de mama en Bucaramanga, Colombia Introducción. El cáncer de mama es un problema de salud pública a nivel mundial y en Santander es la primera causa de morbimortalidad por cáncer en mujeres. Todo cáncer se considera una enfermedad genética y las mutaciones en los genes BRCA confieren un riesgo de 60% a 80% para el cáncer de mama. Este estudio consistió en buscar las dos mutaciones BRCA1 más frecuentes según la base de datos Breast Cancer Core Information. Objetivo. Determinar la presencia de mutaciones específicas (185delAG, exón 2, y 5382insC, exón 20) en el gen BRCA1 en mujeres con cáncer de mama heredo-familiar, atendidas en los diferentes servicios de oncología de Bucaramanga, Colombia. Materiales y métodos. La muestra incluyó 30 pacientes, de las cuales se obtuvo un consentimiento informado, un cuestionario dirigido y sangre venosa para los estudios moleculares. El análisis molecular se realizó mediante PCR-mismatch, para introducir o eliminar sitios de restricción, y digestión enzimática (HinfI o DdeI). Resultados. No se detectaron dos de las mutaciones más frecuentes en el gen BRCA1 en las 30 pacientes estudiadas. Conclusión. Se requieren más estudios en la región que abarquen la tamización de la totalidad del gen BRCA1, para hacer una mayor contribución al conocimiento de la epidemiología molecular del cáncer de mama en Bucaramanga, Santander, Colombia.Palabras clave: neoplasias de la mama/genética, genes relacionados con las neoplasias, genes supresores, genes BRCA1, mutación de línea germinal, predisposición genética a la enfermedad. Mutations in the BRCA1 gene (185delAG and 5382insC) are not present in any of the 30 breast cancer patients analyzed from eastern ColombiaIntroduction. Breast cancer is considered a worldwide public health problem, and, in Santander Province, Colombia, it is the first leading cause of morbidity and mortality by cancer in women. All cancers are considered genetic diseases, and mutations in BRCA (BReast CAncer) genes raises the risk for breast cancer by 60%-80%. The current study searched for the two most frequent BRCA1 mutations reported in the Breast Cancer Core Information database. Objective. The presence of specific mutations (185delAG, exon 2 and 5382insC, exon 20) was determined for the BRCA1 gene in women with familial/hereditary breast cancer. Materials and methods. The sample included 30 female patients using the oncology services in Bucaramanga, eastern Colombia; an informed consent, a questionnaire and a blood sample were obtained from each. The molecular analysis was done with PCR-Mismatch, to detect the insertion or eliminatation of a restriction site, and enzymatic digestion methods (HinfI or DdeI). Results. Two of the most frequent BRCA1 mutations in the international database were not found in the 30 patients studied. Conclusion. Additional mutation screening techniques are necessary involving the entire BRCA1 gen...

Ten X-chromosome short tandem repeats (X-STRs: DXS8378, DXS7132, DXS9898, DXS6809, DXS6789, DXS101, GATA172D05, HPRTB, DXS8377, and DXS7423) were analyzed in a sample of unrelated individuals (108 males and 110 females) from the Santander Department in Colombia. In this sample, gene diversities varied between 63.56%, for DXS8378, and 91.41%, for DXS8377. For this set of 10 X-STRs, a high discrimination power was obtained for both male (1 in 3 x 10(6)) and female (1 in 9 x 10(10)) samples and a high mean exclusion chance in father/daughter duos (99.993%) and in father/mother/daughter trios (99.9999%), demonstrating the usefulness of this set of markers in forensic and kinship analysis. Hardy-Weinberg equilibrium was tested in the female sample and no significant deviations were found. Pairwise analysis showed significant differences in the comparison with samples from Spain, Peru, and Argentina and with African American and Hispanic samples from New York. This same set of X-STRs was also typed in 51 mother/father/daughter trios, 43 mother/son duos, and in a single father/daughter pair. In total, four mutations were observed; one at DXS7132 and at DXS6809, and two at DXS8377. Two mutations were paternal and one maternal; and to a fourth mutation, it was not possible to define its origin.