Reproductive life disorders in Italian celiac women. A case-control study

BACKGROUND: The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. METHODS: The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. RESULTS: 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). CONCLUSIONS: The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders

Polymorphic variants of genes involved in homocysteine metabolism in celiac disease

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size

Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH-related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.A doença celíaca é uma desordem gastrointestinal causada pelo glúten proveniente do trigo, centeio ou cevada. Em pessoas geneticamente predispostas, o glúten induz uma inflamação imune da mucosa do intestino delgado. As lesões histológicas incluem linfocitose intraepitelial, hipertrofia de criptas e atrofia vilosa, resultando em malabsorção de micro- e macronutrientes. O único tratamento para os pacientes celíacos é a restrição permanente de glúten na dieta (GFD).Espécies reativas de oxigênio (ROS) e o estresse oxidativo estão fortemente associados à doença celíaca. O glutatião (GSH) é o principal detoxificante de ROS endógeno ou exógeno no intestino. Para explicar o papel do ciclo redox do glutatião nos pacientes celíacos, nós examinamos as atividades das enzimas GSH-relacionadas e anti-oxidantes (AO) glutatião peroxidase (GPx) e glutatião redutase (GR), assim como a concentração de GHS em biópsias do intestino delgado e sangue periférico de crianças afetadas pela doença celíaca. A concentração dos hidroperóxidos lipídicos (LOOH) como marcadores do dano oxidativo foi medida em várias amostras. Os resultados mostram claramente a mal função significante do ciclo redox do GSH com uma diminuição concomitante da capacidade de regenerar GSH e detoxificar LOOH nos pacientes celíacos, mesmo após vários anos de GFD. A administração oral de GSH e uma dieta rica em anti-oxidantes naturais, assim como de suplementos apropriados na dieta, poderiam ser de grande benefício aos pacientes