Progesterone receptor gene polymorphism and recurrent spontaneous abortion

PURPOSE: to assess a possible association between polymorphism of the progesterone receptor gene (PROGINS) and recurrent spontaneous abortion (RSA). METHODS: in this case-control study, 85 women with at least three previous spontaneous abortions without an identifiable cause (RSA Group) and 157 women with at least two previous term pregnancies without pathologies and no previous miscarriage (Control Group) were selected. An amount of 10 mL of peripheral blood was collected by venipuncture and genomic DNA was extracted by the DTAB/CTAB method, followed by the polymerase chain reaction (PCR) under specific conditions for this polymorphism and by amplification by 2% agarose gel electrophoresis. The bands were visualized with an ultraviolet light transilluminator and the gels were photographed. Differences in the PROGINS genotype and allele frequencies between groups were analyzed by the χ2 test, with the level of significance set at p<0.05. The Odds Ratio (OR) was also used, with 95% confidence intervals 95%CI. RESULTS: PROGINS genotypic frequencies were 72.3% T1T1 and 27.7% T1T2 for the RSA group and 764% T1T1, 22.3% T1T2 and 1.3% T2T2 for the control group. There were no differecnes between groups when the genotype and allele frequencies were analyzed: respectively p=0.48 (OR: 0.8) and p=0.65 (OR: 0.9). CONCLUSIONS: our results suggest that PROGINS polymorphism is not associated with RSA.OBJETIVO: investigar se polimorfismos dos genes que codificam o receptor de progesterona (PROGINS) estão relacionados à ocorrência de aborto espontâneo de repetição (AER). MÉTODOS: em estudo caso-controle, foram selecionados 85 pacientes com antecedente de pelo menos três abortos precoces sem etiologia definida (Grupo Caso) e 157 mulheres com história de pelo menos duas gestações de termo sem intercorrências e sem passado de abortamento (Grupo Controle). Realizada coleta de 10 mL de sangue por punção venosa periférica e extração de DNA pela técnica DTAB/CTAB. As genotipagens foram feitas por reação em cadeia de polimerase (PCR), nas condições de ciclagem específica para o polimorfismo em estudo, seguida de amplificação em gel de agarose a 2%. A visualização das bandas foi feita sob luz ultravioleta e os géis foram fotografados. As diferenças genotípicas e alélicas entre os dois grupos para o polimorfismo PROGINS foram calculadas pelo teste de χ2, adotando-se como nível de significância valores de p<0,05. Calculou-se ainda o Odds Ratio (OR, razão de chances), com intervalos de confiança de 95% (IC95%). RESULTADOS: As frequências genotípicas encontradas para o polimorfismo PROGINS foram de 72,3% T1/T1 e 27,7% T1/T2 no grupo com AER e 76,4% T1/T1, 22,3% T1/T2 e 1,3% T2/T2 no Grupo Controle. Não houve diferenças entre os grupos, analisando-se as frequências genotípicas e alélicas: respectivamente p=0,4 (OR: 0,8) e p=0,6 (OR: 0,9). CONCLUSÕES: os dados do presente estudo sugerem que o polimorfismo PROGINS do gene dos receptores de progesterona não está relacionado ao AER.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Departamento de ObstetríciaUniversidade Federal de São Paulo (UNIFESP)UNIFESP, Depto. de ObstetríciaUNIFESPSciEL

Immunoregulatory gene polymorphisms in women with preeclampsia

The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). the aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (-1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case-control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), Afel (CD28) and AluI (ICOS). Data were analyzed by X(2) or Fisher's exact test; a P-value of < 0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P=0.01 and P=0.01, respectively). We found a significantly lower frequency of the ICOS (-1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms. Hypertension Research (2011) 34, 384-388; doi:10.1038/hr.2010.247; published online 16 December 2010Fundacao de Amparo a PesquisaCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Obstet, BR-01415002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, BR-01415002 São Paulo, BrazilFundacao de Amparo a Pesquisa: 07/57446-0Web of Scienc

Cytokine gene polymorphisms in preeclampsia and eclampsia

The clinical spectrum of preeclampsia ( PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. the biological factors that determine the progression of PE to eclampsia ( E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. the production of cytokines, IL-10 and TGF-beta 1, is apparently suppressed, and altered IL-2/IL-10 and TNF-alpha/IL-10 ratios have been reported in preeclamptic cases. the relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-alpha promoter (-308 G>A), IL6 promoter (-174 G>C), IFN-gamma intron 1 (+874 A>T), IL10 promoters (-1082 A>G), (-819 C>T) and (-592 C>A) and TGF-beta 1 codon 10 (+869 T>C) and codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. the chi(2) or Fisher's exact tests were used to compare genotype frequencies. Among the six single-nucleotide polymorphisms ( SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-gamma (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil. Hypertension Research ( 2009) 32, 565-569; doi: 10.1038/hr.2009.58; published online 1 May 2009Fundacao de Amparo a Pesquisa do Estado de Alagoas (FAPEAL)Universidade Federal de São Paulo, Dept Obstet, BR-04145002 São Paulo, BrazilAlagoas State Univ, Dept Obstet & Gynecol, Alagoas, BrazilUniversidade Federal de São Paulo, Dept Obstet, BR-04145002 São Paulo, BrazilWeb of Scienc

Friction stir welds in aluminium: design S-N curves from statistical analysis of literature data

Appropriate S-N fatigue design curves for friction stir (FS) welded joints in aluminium alloys are currently not specified in design codes and standards. The present paper is intended to assist in enabling standardised fatigue design for such joints, through a comprehensive statistical analysis of more than 500 individual sets of data gathered from published literature. These data are used to establish the usual design fatigue curves for welds that give a 97.7% survival probability with 95% confidence. Experimental fatigue data represent defect-free butt joints and include both flat plate and tubular joints between similar aluminium alloys (across the range of 2xxx, 5xxx, 6xxx, and 7xxx series). Weld conditions include as-welded, machined, and post-weld heat treated under constant amplitude cyclic loading at various stress ratios in the range from R = -1 to 0.5. A systematic comparison is presented by categorising the data according to the alloy type, temper condition, postweld heat treatment and stress ratio and the correlation with the S-N design curves from Eurocode 9 is also considered. The fatigue curves presented in this paper will serve as a useful guideline for engineers involved in design of friction stir aluminium joints subjected to in-service fatigue loading