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Polimorfismos genéticos do VEGF, RAGE, PON1 e PON2 na retinopatia diabética em indivíduos com diabetes tipo 2
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A diabetes mellitus tipo 2 (DM2) é responsável por uma elevada morbilidade e mortalidade em todo o Mundo, essencialmente devido às suas complicações, entre as quais a retinopatia diabética (RD), considerada uma das mais graves, e responsável por 4,8% dos casos de cegueira. Estudos sugerem uma componente genética como um dos principais factores para o desenvolvimento da RD. O gene do VEGF (vascular endothelial growth factor) é um dos mais estudados, por promover a angiogénese e a neovascularização. Outro importante gene candidato é o RAGE (receptor for advanced glycation end products), e, mais recentemente, os genes da paraoxonase, PON1 e PON2. Objectivou-se avaliar a influência dos polimorfismos VEGF -634C/G, RAGE -374T/A, PON1Gln192Arg e PON2Cys310Ser no aparecimento e progressão da RD em indivíduos com DM2 e a sua influência no aparecimento da DM2. Analisaram-se 129 indivíduos, 86 com DM2 e 43 indivíduos saudáveis. Os polimorfismos foram avaliados em todos os indivíduos por PCR-FRLP. A caracterização clínica e a determinação da actividade enzimática da PON1 foram avaliadas em 47 diabéticos. Não se obtiveram diferenças para o polimorfismo do VEGF-634 G/C. O alelo A do polimorfismo RAGE -374A/T mostrou-se mais frequente em indivíduos sem RD ou EMD quando comparados com indivíduos com RD ou EMD. O alelo Q (Gln) e o alelo S (Ser) dos polimorfismos PON1Gln192Arg e PON2Cys310Ser, respectivamente, mostraram-se mais frequentes em indivíduos com DM2 quando comparados com indivíduos saudáveis. Não houve quaisquer diferenças relativamente à actividade enzimática da PON1, nem em relação ao polimorfismo da PON1 nem em relação à presença ou ausência de RD ou EMD. Conclui-se que o alelo A do polimorfismo RAGE -374A/T é factor protector para o aparecimento da RD e do EMD, enquanto os alelos Q e S dos polimorfismos PON1Gln192Arg e PON2Cys310Ser, respectivamente, são factores de risco para o aparecimento da DM2.
Type 2 diabetes mellitus (DM2) is responsible for high morbidity and mortality rates worldwide, mainly due to its complications, including diabetic retinopathy (DR), considered one of the most serious, and responsible for 4.8% of all cases of blindness. Studies suggest a genetic component as a major factor for the development of DR. The VEGF gene (vascular endothelial growth factor) is one of the most studied, due to its role in promoting angiogenesis and neo-vascularization. Another important candidate gene is RAGE (receptor for advanced glycation end products), and, more recently, paraoxonase genes, PON1 and PON2. Our aim was to evaluate the influence of the VEGF -634C/G, RAGE -374T/A, PON1 Gln192Arg and PON2 Cys310Ser polymorphisms on the onset and progression of DR in individuals with DM2, and its influence on the onset of DM2. We analyzed 129 subjects, 86 with DM2 and 43 healthy subjects .Polymorphisms were assessed in all subjects by PCR-RFLP. Clinical evaluation and PON1 enzymatic activity were evaluated in 47 diabetics. No differences were obtained for the VEGF -634G/C polymorphism. The RAGE -374A/T A allele was more frequent in individuals without DR or diabetic macular edema (DME) when compared with individuals with DR or DME. The Q allele (Gln) and the S allele (Ser) of PON1Gln192Arg and PON2Cys310Ser polymorphisms, respectively, were more frequent in individuals with DM2 compared with healthy subjects. There were no differences in the enzymatic activity of PON1, either concerning the PON1 polymorphism or the presence or absence of DR or DME. We conclude that the RAGE-374A/T A allele seems to protect patients with DM2 against the development of DR and DME, while the Q and S alleles of the PON1 Gln192Arg and PON2Cys310Ser polymorphisms, respectively, seem to be risk factors for the development of DM2
Type 2 diabetes mellitus (DM2) is responsible for high morbidity and mortality rates worldwide, mainly due to its complications, including diabetic retinopathy (DR), considered one of the most serious, and responsible for 4.8% of all cases of blindness. Studies suggest a genetic component as a major factor for the development of DR. The VEGF gene (vascular endothelial growth factor) is one of the most studied, due to its role in promoting angiogenesis and neo-vascularization. Another important candidate gene is RAGE (receptor for advanced glycation end products), and, more recently, paraoxonase genes, PON1 and PON2. Our aim was to evaluate the influence of the VEGF -634C/G, RAGE -374T/A, PON1 Gln192Arg and PON2 Cys310Ser polymorphisms on the onset and progression of DR in individuals with DM2, and its influence on the onset of DM2. We analyzed 129 subjects, 86 with DM2 and 43 healthy subjects .Polymorphisms were assessed in all subjects by PCR-RFLP. Clinical evaluation and PON1 enzymatic activity were evaluated in 47 diabetics. No differences were obtained for the VEGF -634G/C polymorphism. The RAGE -374A/T A allele was more frequent in individuals without DR or diabetic macular edema (DME) when compared with individuals with DR or DME. The Q allele (Gln) and the S allele (Ser) of PON1Gln192Arg and PON2Cys310Ser polymorphisms, respectively, were more frequent in individuals with DM2 compared with healthy subjects. There were no differences in the enzymatic activity of PON1, either concerning the PON1 polymorphism or the presence or absence of DR or DME. We conclude that the RAGE-374A/T A allele seems to protect patients with DM2 against the development of DR and DME, while the Q and S alleles of the PON1 Gln192Arg and PON2Cys310Ser polymorphisms, respectively, seem to be risk factors for the development of DM2
Descrição
Tese de mestrado, Doenças Metabólicas e Comportamento Alimentar, Faculdade de Medicina, Universidade de Lisboa, 2013
Palavras-chave
Diabetes mellitus tipo 2 Retinopatia diabética Edema macular diabético Predisposição genética Teses de mestrado - 2013