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Caracterização do polimorfismo no gene de susceptibilidade para a enxaqueca STX1A : estudo numa população controlo da ilha de São Miguel (Açores)
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Abstract(s)
A enxaqueca é uma doença multifatorial, que resulta de complexas interações entre fatores genéticos e ambientais, apresentando dois principais subtipos, a enxaqueca com e sem aura. A causa exata da enxaqueca é ainda desconhecida, mas já está estabelecido que fatores genéticos estão na sua base. A natureza complexa da doença faz com que poucos genes de susceptibilidade tenham sido identificados e replicados de forma consistente. O gene STX1A é responsável pela produção da proteína sintaxina 1A. Esta proteína regula a libertação dos neurotransmissores no sistema nervoso central e interage com o transportador da serotonina. A serotonina influência quase todas as funções cerebrais, incluindo a estimulação do ácido gama-aminobutírico. Alguns recetores agonistas do ácido gama-aminobutírico são utilizados na profilaxia da enxaqueca. A investigação realizada consistiu na replicação de parte de um estudo empreendido na população de Portugal Continental, no qual se associaram à enxaqueca vários tagging SNPs do gene STX1A (Lemos et al., 2010). A amostra analisada no estudo foi constituída por 103 indivíduos, sem enxaqueca, da ilha de São Miguel- Açores. Analisaram-se, por PCR-RFLP e sequenciação, 3 SNPs (rs941298, rs6951030 e rs3793243) do gene STX1A. Os alelos mais frequentes para o rs941298 e para o rs6951030 são os mesmos da população do Norte de Portugal (C e T). Para o rs3793243 constatou-se que o alelo mais frequente na população açoriana é o T e na população continental é o alelo C. Para os rs941298 e rs6951030 a frequência dos alelos de risco T e G, em São Miguel é bastante semelhante à frequência destes mesmos alelos na população de Portugal Continental. As frequências genotípicas obtidas para os rs941298,rs6951030 e rs3793243 foram 49,5%, 56,3% e 54,5%, respetivamente. As frequências genotípicas estavam em conformidade com o equilíbrio de Hardy-Heinberg. Os valores de diversidade genética obtidos para os 3 SNPs variaram entre 0,172 e 0,454. O haplótipo C-C-T foi o mais frequente na ilha de São Miguel, sendo o haplótipo T-T-T o que apresenta uma maior frequência na população de Portugal Continental. O haplótipo C-T-G foi o menos frequente em ambas as populações. Uma vez que o perfil alélico e genotípico dos indivíduos sem enxaqueca foi muito semelhante em São Miguel e Portugal Continental, comprovasse a homogeneidade entre estas duas populações. Assim, é possível concluir com este trabalho que a amostra selecionada de indivíduos sem enxaqueca, pode vir a ser utilizada como amostra controlo. A semelhança entre esta amostra e a de Portugal Continental permitirá, no futuro, prosseguir a investigação sobre a enxaqueca, incluindo a replicação do estudo de Lemos et al. (2010) com o gene STX1A.
ABSTRACT: Migraine is a multifactorial disease that results from complex interactions between genetic and environmental factors, presenting two main subtypes, migraine with and without aura. The exact cause of migraine is unknown, but an important role of genetic factors is already established. The complex nature of the disease implies that a reduced number of susceptibility genes has been identified and consistently replicated. The STX1A gene encondes for the protein syntaxin 1A. This protein regulates the release of neurotransmitters in the central nervous system and interacts with the serotonin transporter. Serotonin influences many brain functions, including the stimulation of gamma-aminobutyric acid. Some agonists receptors of the gamma-aminobutyric acid are used in the prophylaxis of migraine. The present work consisted in the replication of part of a study undertaken in the Portuguese Mainland population, in which tagging SNPs of the STX1A gene were associated with migraine gene (Lemos et al., 2010). One-hundred and three individuals without migraine, born in the island of São Miguel-Azores were included in the study. Three SNPs of the STX1A gene (rs941298, rs6951030 and rs379324) were analyzed by PCR-RFLP and sequencing. For the rs941298 and rs6951030 the most frequent alleles were the same as those found in Mainland Portugal (C and T). The most frequent allele for rs3793243 in the Azorean population was T, whereas in the continental population it was allele C. For the polymorphisms rs941298 and rs6951030 the frequency of the risk alleles T and G is very similar in San Miguel comparatively to the frequency of these same alleles in the population of mainland Portugal. The genotypic frequencies for obtained for rs941298, rs6951030 and rs3793243 were 49.5%, 56.3% and 54.5%, respectively. Genotype frequencies were in conformity with Hardy-Weinberg expectations. The values obtained for genetic diversity for the 3SNPs varied between 0.172 and 0.454. The most frequente haplotype in the Azorean sample was C-C-T, whereas the T-T-T haplotype showed a higher frequency in the population of continental Portugal. The C-T-G haplotype was the least frequent in both populations. Since the allelic and genotypic profile of the individuals without migraine was very similar between the Azorean sample analyzed and mainland Portugal, it was possible to show the homogeneity between the two populations. Therefore, we conclude that the sample of individuals without migraine analyzed in this study can be used as controls for future work, including the replication of the study of Lemos et al. (2010) with the gene STX1A.
ABSTRACT: Migraine is a multifactorial disease that results from complex interactions between genetic and environmental factors, presenting two main subtypes, migraine with and without aura. The exact cause of migraine is unknown, but an important role of genetic factors is already established. The complex nature of the disease implies that a reduced number of susceptibility genes has been identified and consistently replicated. The STX1A gene encondes for the protein syntaxin 1A. This protein regulates the release of neurotransmitters in the central nervous system and interacts with the serotonin transporter. Serotonin influences many brain functions, including the stimulation of gamma-aminobutyric acid. Some agonists receptors of the gamma-aminobutyric acid are used in the prophylaxis of migraine. The present work consisted in the replication of part of a study undertaken in the Portuguese Mainland population, in which tagging SNPs of the STX1A gene were associated with migraine gene (Lemos et al., 2010). One-hundred and three individuals without migraine, born in the island of São Miguel-Azores were included in the study. Three SNPs of the STX1A gene (rs941298, rs6951030 and rs379324) were analyzed by PCR-RFLP and sequencing. For the rs941298 and rs6951030 the most frequent alleles were the same as those found in Mainland Portugal (C and T). The most frequent allele for rs3793243 in the Azorean population was T, whereas in the continental population it was allele C. For the polymorphisms rs941298 and rs6951030 the frequency of the risk alleles T and G is very similar in San Miguel comparatively to the frequency of these same alleles in the population of mainland Portugal. The genotypic frequencies for obtained for rs941298, rs6951030 and rs3793243 were 49.5%, 56.3% and 54.5%, respectively. Genotype frequencies were in conformity with Hardy-Weinberg expectations. The values obtained for genetic diversity for the 3SNPs varied between 0.172 and 0.454. The most frequente haplotype in the Azorean sample was C-C-T, whereas the T-T-T haplotype showed a higher frequency in the population of continental Portugal. The C-T-G haplotype was the least frequent in both populations. Since the allelic and genotypic profile of the individuals without migraine was very similar between the Azorean sample analyzed and mainland Portugal, it was possible to show the homogeneity between the two populations. Therefore, we conclude that the sample of individuals without migraine analyzed in this study can be used as controls for future work, including the replication of the study of Lemos et al. (2010) with the gene STX1A.
Description
Dissertação de Mestrado em Ciências Biomédicas.
Keywords
Doença Neurológica Enxaqueca Genética Gene STX1 Migraine Multifactorial Disease
Citation
Ponte, Lisete Margarida Martins – "Caracterização do polimorfismo no gene de susceptibilidade para a enxaqueca STX1A : estudo numa população controlo da ilha de São Miguel (Açores)". Ponta Delgada : Universidade dos Açores. 2012. VI, 61 p.. Dissertação de Mestrado.