Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu's arteritis.

BACKGROUND: Takayasu's arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA. METHODS: We analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; CASES: aortic tissues of individuals with Takayasu's arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis). RESULTS: Of 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found. CONCLUSION: We identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.

PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study.

The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.

Participaçao dos genes de classe II do principal sistema de histocompatibilidade (MHC) na suscetibilidade a enfermidades auto-imunes / Participation of the class II genes of major histocompatibility complex (MHC) in the susceptibility to autoimmune diseases

A participaçao dos antígenos do maior complexo de histocompatibilidade (MHC) na suscetibilidade a certas doenças é ainda mal conhecida. Apesar disso, atualmente, graças a novas técnicas de tipificaçao tanto sorológicas como moleculares, tem sido possível um melhor conhecimento dos mecanismos envolvidos neste fenômeno, que é um dos grandes enigmas da biologia e medicina modernas. Até hoje, existem mais de 70 enfermidades associadas a antígenos do MHC, as quais têm sido classificadas, basicamente, em dois grupos. O primeiro inclui as espondiloartropatias associadas ao HLA-B27, o segundo, as doenças associadas a vários antígenos da regiao HLA-D, a maioria das quais é de origem auto-imune. Nesta revisao, ao lado de informaçoes gerais sobre o MHC e sua participaçao na fisiopatologia das doenças, sao estudados em particular o diabete melito insulino-dependente, a artrite reumatóide, a enfermidade celíaca e o pênfigo vulgar. Como conclusoes: na maioria dos casos de associaçao de doenças com moléculas de classe II, a suscetibilidade é dada por mais de um alelo e, inclusive, por haplótipos; estes alelos ou haplótipos podem ser importantes na suscetibilidade por si mesmos ou ser unicamente marcadores de um terceiro alelo de suscetibilidade; este terceiro alelo pode ser do mesmo sistema HLA ou um alelo nao HLA que se encontre em desequilíbrio de uniao com este conjunto de genes. Na maioria dos casos estudados, a suscetibilidade ou resistência à enfermidade nao pode ser explicada pela participaçao de alelos únicos ou resíduos de aminoácidos, senao pela participaçao de vários alelos, inclusive haplótipos completos. Estes alelos podem ser diretamente incriminados, uma vez que apresentam um determinante estrutural único, o qual está associado à doença. Por outro lado, estes alelos poderiam ser somente marcadores de um terceiro alelo de suscetibilidade, HLA ou nao HLA, em desequilíbrio de uniao. Se estes alelos ou haplótipos estao envolvidos diretamente na suscetibilidade à doença, pode dever-se à sua açao na apresentaçao antigênica e na seleçao do repertório da célula T, ambos fenômenos importantes no estabelecimento da tolerância e, portanto, na auto-imunidade