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Previous issue date: 2016-09-26 / Metabolic syndrome (MS) is a complex disorder with a strong genetic basis and multifactorial etiology. Insulin resistance (IR) causes MS and it can be triggered by intestinal inflammation like the use of lactose in patients intolerant of this carbohydrate. It was found that variants in the lactase gene are associated with lactase non persistence LNP and MS in a population sample of Salvador/Bahia; and whether these variants are modifying the response to diet-therapeutic intervention in patients with this syndrome; also compared the biochemical test of lactose tolerance (LTT) with genetic diagnosis; and tested the association of mutations in the lactase gene with cofactors SM (TGL, HDL-C, blood pressure, glucose levels, waist circumference), with anthropometric variables (Arm Circumference, Body Mass Index, Hip Circumference, hip-waist ratio,lean massand fat mass percentages) and other factors associated with MS: insulin, total cholesterol, LDL-C, VLDL-C, C-reactive protein, HOMA-IR, renal function (creatinine, urea, uric acid, microalbuminuria) and vitamin D. There were two studies: a case-control with 257 cases (MS) and 210 controls and other clinical trial study, which was conducted with three types of diet in patients with metabolic syndrome: diet 1 - No lactose; Diet 2 - Lactose and energy restriction; Diet 3 - Only energy restriction. In all groups were also evaluated for nine SNPs in the lactase (LCT) gene. The genotyping of SNPs was carried out by TaqMan assays. Data were analyzed using SPSS, 20.0, and the Hardy-Weinberg Equilibriumhaplotype frequencies were calculated using Arlequin, 2000 program. The results showed that all diets improve several MSaspects after two months of intervention, especially in the diet 1, that also decreased inflammation, insulin resistance and dyslipidemia (LDL-C). In addition,it was the diet that most took out patients of the MS: 2.72 times more likely to get out of MS than diet 3. LNP was high in both cases and controls. There was compatibility between clinical diagnosis for LNP by Lactose Tolerance Test and two of the studied SNPs, they were rs4988253 and rs182549, those that have proved functional studies. Thus, it is suggested the analysis of LCT gene polymorphisms before the nutritional therapeutics for patients with MS, as well as to take out the lactose in their diet. / A S?ndrome Metab?lica (SM) ? uma desordem complexa, de forte base gen?tica e de etiologia multifatorial. Dentre as suas causas, encontra-se a Resist?ncia ? Insulina (RI) que pode ser desencadeada pela inflama??o intestinal, pelo uso de lactose em pacientes intolerantes a este carboidrato. Verificou-se quais variantes no gene da lactase est?o associados ? IL e SM em amostra da popula??o de Salvador/Bahia; e tamb?m se estas variantes s?o modificadoras da resposta ? interven??o dietoter?pica em portadores desta s?ndrome; comparou-se tamb?m o teste bioqu?mico de toler?ncia ? lactose (TTL) com o diagn?stico gen?tico; e testou-se a associa??o das muta??es no gene da lactase com os cofatores da SM (TGL, HDL-c, press?o arterial, glicemia, circunfer?ncia da cintura), com vari?veis antropom?tricas (circunfer?ncia do bra?o, ?ndice de massa corporal, circunfer?ncia do quadril, raz?o cintura quadril, percentual de massa magra e massa gorda) e com outros fatores associados ? SM: insulina, colesterol total, LDL-C, VLDL, Prote?na C reativa, HOMA-IR, fun??o renal (creatinina, ur?ia, ?cido ?rico, microalbumin?ria) e vitamina D. Foram realizados dois estudos: um caso-controle com 257 casos (SM) e 210 controles e outro estudo de tipo ensaio cl?nico, que foi realizado com tr?s tipos de dieta com os pacientes com SM: dieta 1 ? sem lactose; dieta 2 ? sem lactose e com restri??o energ?tica; Dieta 3 ? apenas restri??o energ?tica. Em ambos os grupos tamb?m foram avaliados 9 SNPs no gene da lactase. A genotipagem dos SNPs foi realizada pela tecnologia de ensaios TaqMan. Os dados foram analisados pelo programa SPSS ver 20.0 e a adequa??o das frequ?ncias genot?picas ao Equilibrio de Hardy-Weinberg e c?lculo da frequ?ncia dos hapl?tipos formados pelos polimorfismos foram obtidos atrav?s do programa Arlequin ver 2000. Os resultados mostraram que todas as dietas melhoram o quadro da SM ap?s dois meses de interven??o, com destaque para a dieta 1, que tamb?m diminuiu a inflama??o, resist?ncia ? insulina e a dislipidemia (LDL-C). Al?m disso foi a dieta que mais tirou paciente da SM: apresentou 2,72 vezes mais chances de sair da SM que a dieta 3. A intoler?ncia ? lactose foi alta tanto em casos como em controles. Houve compatibilidade do TTL com os SNPsrs4988253 e rs182549, os ?nicos que possuem estudos funcionais. Assim, sugere-se an?lise de polimorfismos do gene da lactase antes da prescri??o nutricional para pacientes com SM, bem como, a retirada da lactose da dieta.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.uefs.br:8080:tede/528 |
| Date | 26 September 2016 |
| Creators | Ara?jo, Edilene Maria Queiroz |
| Contributors | Rios, Domingos L. de S. |
| Publisher | Universidade Estadual de Feira de Santana, Doutorado Acad?mico em Biotecnologia, UEFS, Brasil, DEPARTAMENTO DE CI?NCIAS BIOL?GICAS |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UEFS, instname:Universidade Estadual de Feira de Santana, instacron:UEFS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | -5520924549352904568, 600, 600, 600, -6971480722008537872, -5518144268585252051 |
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