Abnormal folate/homocysteine metabolism due to polymorphisms in genes involved in this pathway has been implicated as an etiologic factor in Down syndrome (DS). This case-control study aimed to evaluate the effect of maternal C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) as risk factors for the development of DS and congenital heart defects (CHD). The distribution of these genotypic variants was similar between mothers of children with DS (n = 239) and control mothers of normal children (n = 197), but the combined genotypes 677CT or TT and 1298AA increased the risk of having offspring with DS (OR = 1.99; 95% CI 1.11-3.55). The presence of the 677T allele in case mothers resulted in a 2.07-fold higher odds of CHD in the offspring (P < 0.01). Among the 57 mothers of CHD-affected children with DS who carried the MTHFR 677CT or TT genotypes and did not have periconceptional folic acid intake, we observed a 2.26-fold increased odds (95% CI 1.25-4.09) of having any CHD-affected child with DS. Our results show that MTHFR genetic polymorphisms may be involved in the etiology of DS in our population when controlling for age. We noted a borderline significant association for the C677T polymorphism (P = 0.05). Maternal 677T allele may be associated with an increased occurrence of CHD in children with DS and we anticipate that women who carry this polymorphism would benefit from periconceptional folic acid supplementation. (c) 2009 Wiley-Liss, Inc.

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Diabetic complications are frequent among out patients referring to general hospitals. Almost all patients presented at least one risk factor for cardiovascular disease, justifying the efforts for identification and adequate control.

Biochemical markers of cellular stress/injury have been proposed to indicate outcome after head injury. The aim of the present study was to determine whether plasma von Willebrand factor (VWF) levels correlate with primary outcome and with clinical variables in severe traumatic brain injury (TBI). Forty-four male patients, victims of severe TBI, were analyzed. Clinical outcome variables of severe TBI comprised survival and neurological assessment using the Glasgow Outcome Scale (GOS) at intensive care unit (ICU) discharge. Computerized tomography (CT) scans were analyzed according to Marshall CT classification. Three consecutive venous blood samples were taken: first sample (11.4 +/- 5.2 h after trauma, mean +/- SD), and 24 h and 7 days later. The result of mean plasma VWF concentration was significantly higher in the TBI group (273 U/dL) than in the control group (107 U/dL; p < 0.001). Severe TBI was associated with a 50% mortality rate. Nonsurvivors presented significantly higher APACHE II scores than survivors (nonsurvivors mean, 18.8; survivors mean, 12.7; p < 0.001), and also presented higher scores in Marshall CT classification (nonsurvivors mean, 4.6; survivors mean, 2.7; p < 0.05). There was a significant positive correlation between plasma levels at second plasma sampling and scores in Marshall CT classification (p < 0.05). The sensitivity of plasma VWF concentration in predicting mortality according to the cut-off of 234 U/dL was 64%, with a specificity of 68%. Therefore, VWF increases following severe TBI may be a marker of unfavorable outcome.

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Non-syndromic cleft lip and palate (CL/P) occurs due to interaction between genetic and environmental factors. Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway. Because of the involvement of MTHFR, MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for CL/P, we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study. The analyses involved 114 non-syndromic phenotypically white children with clefts (case) and 110 mothers, and 100 non-affected (control) children and their mothers. The polymorphisms 677C>T of MTHFR, 2756A>G of MTR, and 66A>G of MTRR genes were analyzed by PCR-RFLP. Allelic frequencies did not differ from other studies conducted on white populations for MTHFR 677T allele (0.35) and for MTR 2756G allele (0.17), but MTRR 66G allele frequency (0.35) was lower than observed elsewhere. The genotypic distribution of the 677C>T polymorphisms under study did not show significant differences between CL/P patients, their mothers and controls. These results suggest that the alterations of folate metabolism related to these polymorphisms are not involved in clefting in the population under study.

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SummaryThe aims of this study were to investigate the contributions of the mitochondrial DNA m.4216T > C and m.4917A > G variants, and also of the European-specific mitochondrial cluster J/T, to the development of type 2 diabetes mellitus in Caucasian-Brazilian patients from Southern Brazil. We analyzed 347 type 2 diabetes patients and 350 control subjects. Variant frequencies in patients and control subjects were compared using χ 2 tests or odds ratio. We also compared clinical and laboratory characteristics among patients with and without the variants. We found that the frequencies of the m.4216T > C and m.4917A > G variants are higher in diabetic patients than in control subjects. Moreover, haplogroups J (partially defined by the presence of the m.4216T > C variant only) and T (partially defined by the presence of both m.4216T > C and m.4917A > G variants) are more frequent in the type 2 diabetic group than in the control group. Patients belonging to the cluster J/T are more insulin resistant than patients of other haplogroups. In conclusion, our results indicate the association of the cluster J/T (as suggested by analyses of the m.4216T > C and m.4917A > G variants) with insulin resistance and type 2 diabetes.