The renin-angiotensin system (RAS) is a hormonal signaling mechanism widely known as a blood pressure regulation system. The classic pathway begins with the release of renin (REN), an aspartyl-protease that cleaves angiotensinogen (AGT) to produce angiotensin I (AngI), which is later hydrolyzed by the angiotensin I-converting enzyme (ACE) to produce angiotensin II (AngII); this octapeptide exerts its functions through its specific receptors, angiotensin II receptor type 1 and type 2 (AGTR1 and AGTR2 respectively). 1 Most of the physiological effects such as blood vessel constriction have been attributed to the AGTR1 signaling pathway. In recent years, however, research papers have described mitogenic and angiogenic activities as well, activities that are also mediated through AGTR1. 2,3 Since angiogenesis and proliferative processes are related to the development, progression and metastasis of cancer, it is reasonable to believe that RAS may have a role in cancer. 4 When ACE insertion-deletion (indel) polymorphism was examined as a cancer risk marker, it was associated with gastric, endometrial, prostate and breast cancer. [5][6][7][8][9][10][11][12][13] However, three different AGTR polymorphisms presented contradictory results when studied for breast cancer. [13][14][15] For every biological system each component contributes to the overall effect; therefore, to explain any phenomenon, a more integrated approach is needed. To date, no study has included more than two RAS genes. With this in mind, in the present work we explored the association between breast cancer and some of the major polymorphisms of the four Abstract Recent information has revealed new roles in the angiogenic processes linked to the rennin-angiotensin system. To date few studies have been done on the association between RAS genes and cancer and the majority focus mainly on angiotensin I-converting enzyme (ACE). For breast cancer there are three reports that include the angiotensin II receptor, subtype 1 (AGTR1), only one for angiotensinogen (AGT) and none for renin gene (REN). In the present study we investigate whether REN (BglI), AGT (M235T), ACE (A245T, Indel), and AGTR1 (A1166C) are associated with breast cancer. Polymorphisms were analysed by PCR and RFPLs or sequence specific assay in three groups: breast cancer, benign breast disease (BBD) and general population. REN polymorphism shows that homozygous for A allele have an increased risk for BBD. Differences in M235T genotype frequencies were significant with less heterozygous in breast cancer. With different risk values ACE indel was associated with BBD and breast cancer. Association of AGTR1 was observed only in the breast cancer group, where C allele carriers present a reduced risk. Results of this work supports previous observations on the possible involvement of this system in breast cancer but it also suggests a role in benign disease.
Human breast cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. There are two polymorphic sites for the restriction enzymes BglII and EcoRI, both detectable by Southern blot analysis. Although the BglII site has been analyzed for loss of heterozygosity, the biallelic EcoRI site polymorphism has not been studied in association with breast cancer, complications or metastasis. We analyzed EcoRI site allele frequencies in Mexican patients with breast cancer, using polymerase chain reaction -restriction fragment length polymorphisms. The polymorphic allelic frequencies in the cases and reference groups were 0.4215 and 0.3375, respectively; this difference was not statistically significant (chi2=0.8687, p=0.3512). Thus, EcoR1 polymorphic site was not associated with breast cancer in this series, but could be analyzed in association with metastases and might be informative in the evaluation of loss of heterozygosity in women with breast cancer.
Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype.
This study compares the detection of Mycobacterium tuberculosis through bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and polymerase chain reaction (PCR) carried out with DNA taken directly from various types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15 cerebrospinal fluid, and 27 of other types) from 160 patients with any form of suspected tuberculosis who came to the Clinical Pathology Laboratory of the Specialties Hospital of the Western National Medical Center of the Mexican Social Security Institute. In all cases Ziehl-Neelsen stains were done, as were also cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285 base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12 (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1 (0.4%) negative with the PCR and positive with the culture. Using the culture as the reference test, the PCR provided a sensitivity of 92.3%, a specificity of 78.7%, a positive predictive value of 20.3%, and a negative predictive value of 99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent to four or five mycobacteria. Also in comparison with the culture, the PCR correctly identified the totality of the mycobacteria of the M. tuberculosis complex. Taking the culture as the reference test, when analyzing just the sputum samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%, a positive predictive value of 52.6%, and a negative predictive value of 98.7%. The PCR is a sensitive and specific technique for detecting the M. tuberculosis complex in both positive and negative bacilloscopy samples. A controlled PCR procedure makes it possible to establish or to exclude the diagnosis of tuberculosis in a time that is reduced from more than three weeks to just 24 to 48 hours. This is particularly useful when an early diagnosis is needed to establish a patient's prognosis or in organ transplant cases.
2 Winter RM, Baraitser M, Douglas JM. A computerised data base for the diagnosis of rare dysmorphic syndromes. J Med Genet 1984;21:121-3. 3 Winter RM, Clarke RD, Ashley K, Gibbs G. A combinatorial method for grouping cases with multiple malformations. J Med Genet (in press). 4 Baraitser M, Winter RM. Iris coloboma, ptosis, hypertelorism
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