Determination of risk factors for cardiovascular disease in Turner Syndrome patients considering clinical and genetic evaluation

• Grant number: 08/03597-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2008
• End date: March 31, 2011
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ieda Therezinha Do Nascimento Verreschi
• Grantee: Ieda Therezinha Do Nascimento Verreschi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Turner Syndrome (TS) is one of the most common chromosomal abnormalities, present at 1:2000 born alive children with a female phenotype. Is characterized citogenetically as a monosomy of the sexual chromosome X (45,X), observed in 50-60% of the cases and the affected individuals present a extremely variable phenotype. In Brazil, the cardiovascular disease (CVD) is a great public health problem and corresponds to almost one third of all death causes. Epidemiologic studies show a reduction of until 13 years on the life expectance of TS patients as compared to the normal women and constitutes the main cause of death in TS. Risk factors to CVD, as sistemic arterial hipertension (SAH) and glicidic metabolism abnormalities were increased in this syndrome, but other factors as lipidic perfil and mainly the distribution and influence of body fat mass were not enough investigated until now. An interesting aspect remain on the identification of the parental origin of chromosome X present in the TS pacient, that is related to many factors as stature, concentration of visceral fat, on dyslipidemies and on cardiovascular abnormalities.The relationship between lipidic perfil and the incidence of CVD are well stablished. However, the frequecy of the abnormal lipidic pattern associated to CVD in TS is not clear. Apolipoprotein E has a crucial role on plasmatic proteins metabolism and acts as binding to the low density lipoprotein (LDL) receptor, that has a role in the intestinal colesterol absortion. This gene has many isoforms and some of then has been related to the decrease of longevity, to greater plasmatic levels of LDL and cholesterol and to increase the incidence of CVD and Alzheimer's disease.Polymorphisms of MTHFR gene can generate defects on folate metabolism and consequently on the level of homocistein and has been considered as genetic factors determining of the CVD.SAH has a prevalence of 20-50% on TS. Is a known risk factor on aterosclerotic process, on myocardic isquemia, on the genesis of cerebral vascular injuries and aortic abnormalities, probably caused by vascular anomalies genetically determined. Polymorphisms of TAP1 gene has an important role on endothelial disfunction, increasing the susceptibility to hypertension disease. The intolerance to glucose has been found until 43% of TS cases. Its well known that GH and hormone replacement therapies may have some unfavourable consequences to women with TS. Genetic factors may contribute to the insulin resistence, as gene ENPP1, that inhibits the insulin receptor activation and which polymorphisms have been related to diabetes and obesity. TS patients have different body proportions related to the normal population and the main difference remains on the proportional reduction of members and body. The index of body mass, elaborated for a normal population, show an increase ratio for TS. Bioimedanciometry is another method used to evaluate the body mass in TS that, added to mathematic calculi of information as age, sex, body mass and height may be processed and compared to methods of high sensitivity as densitometry and hydrometry and generate relations validated to estimate the body composition of specific groups as children, atlets and aged, for instance.This way, analysing genetic, molecular, biochemical, clinic and antropometric characteristics we wish to contribute to increase the understanding of the factors involved on increased risk of CVD in TS. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, KELLY C.; VERRESCHI, IEDA T. N.; SUGAWARA, EDUARDO K.; SILVA, VANESSA C.; GALERA, BIANCA B.; GALERA, MARCIAL FRANCIS; BIANCO, BIANCA; LIPAY, MONICA V. N.. C677T and A1298C Polymorphisms of MTHFR Gene and Their Relation to Homocysteine Levels in Turner Syndrome. GENETIC TESTING AND MOLECULAR BIOMARKERS, v. 16, n. 5, p. 396-400, MAY 2012. (08/03597-0)

GUEDES, ALEXIS D.; BIANCO, BIANCA; LIPAY, MONICA V. N.; CALLOU, EMMANUELA Q.; CASTRO, MARISE L.; VERRESCHI, IEDA T. N.. Uma equação de bioimpedanciometria específica para predição de composição corporal na síndrome de Turner. Arquivos Brasileiros de Endocrinologia e Metabologia, v. 54, n. 1, p. 24-29, FEB 2010. (08/03597-0)