Sugere-se que pacientes na pós-menopausa com DP e osteoporose denotam maior risco de progressão da DP, uma vez que nessa fase ocorre deficiência de estrógeno, podendo aumentar a progressão da DP, seja pelo aumento da expressão de citocinas osteotrópicas ou pela diminuição do osso alveolar102.
A deficiência de estrógeno leva a uma aceleração da reabsorção óssea, característica da osteoporose na pós-menopausa. A terapia de reposição hormonal (TRH) com estrógeno é considerada a terapia de primeira linha para a prevenção da osteoporose em mulheres103.
Estudos revisados na tabela 3 investigaram o papel da TRH em mulheres após a menopausa na periodontite. Eles foram unânimes ao apontar algum efeito benéfico sobre a DP74,76,77,80, seja pela redução da: inflamação gengival74, perda de inserção clínica74,76,80 e perda óssea alveolar76. Além disso, foi verificada maior chance
de DP em mulheres após a menopausa sem uso de TRH do que aquelas na pré- menopausa77. Relata-se o fato de que o estrógeno inibe a expressão de várias citocinas responsáveis pela liberação de osteoclastos sob condições inflamatórias102, minimizando a perda óssea.
Com relação à perda dentária, Haas et al.77 não observaram diferenças,
enquanto Jönsson et al.80 verificaram menor perda dentária em mulheres pós-menopausa
em uso da TRH; porém, no último estudo, as mulheres também faziam uso de altas doses de vitamina D, o que, segundo os autores, poderá otimizar os efeitos antagônicos da TRH à DP80. O uso estrógeno em mulheres na menopausa pode promover proteção contra a perda dentária, mediante a redução da inflamação dos tecidos periodontais, não tendo sido verificado aumento da altura do osso alveolar, nem diminuição da porosidade deste104.
Deficiências, tanto de estrógeno como de testosterona são relacionadas como fator de risco para a osteoporose105. Estudo longitudinal, incluído nesta revisão, abordou a associação entre esteroides sexuais (testosterona e estradiol) e a saúde periodontal em homens idosos75. Sabe-se que existe uma correlação entre o gênero
fatores não foram associados com o uso de esteroides sexuais no estudo há pouco citado75.
Dois estudos revisados na tabela 3 abordaram a presença de receptores de estrógeno (ERs) em tecidos gengivais de sítios saudáveis e doentes29 e de mulheres nas
fases de pré e pós-menopausa78 e verificaram que o ER foi o receptor predominante em amostras de tecidos gengivais saudáveis e doentes, sem diferenças entre homens e mulheres29. A redução da expressão de ER foi verificada no tecido gengival de mulheres
com PC na pós-menopausa78, o que os autores explicaram como resultado de mudanças
inflamatórias ocorrentes nos tecidos gengivais78.
O uso de hormônios contraceptivos por mulheres durante a vida reprodutiva, ao contrário do emprego durante a menopausa, é considerado por influenciar a progressão da DP107. Domingues et al.79 avaliaram o efeito de baixas doses orais de contraceptivos à base de progestina e estradiol e confirmaram a influência negativa destes nas condições periodontais.
Polimorfismos
Um dos estudos revisados na tabela 4 investigou a associação do polimorfismo do gene ERα em pacientes com PAg e PC e verificou uma relação entre
polimorfismo genético no gene ERα e PC em mulheres chinesas81. Outro estudo
investigou polimorfismos no gene ERα também em mulheres chinesas com PC, mas na
condição de pós-menopausa, e encontrou correlação deste com variações na densidade óssea mineral62.
Taguchi et al.108 encontraram associação entre polimorfismo genético no
gene ERα com perda dentária em mulheres japonesas na pós-menopausa, mas as perdas
não foram diretamente correlacionadas à condição periodontal.
Artigo utilizando estudo associação ampla do Genoma (GWAS) identificou uma região genômica no gene ERα relacionado com DP109. O GWAS é um método com
grande poder de identificação de variantes genéticas associadas a um risco elevado de desenvolvimento de uma determinada doença110. Assim, o gene humano ERα (ESR1) pode desempenhar um papel na PC109.
Dentre as limitações para comparações entre os estudos mostrados nesta revisão, pode-se mencionar o fato de que, em sua maioria, os estudos publicados são do tipo transversal, com amostra composta em sua maioria por pacientes portadores de PC. Existe também muita variabilidade nos desenhos experimentais. Poucos estudos
investigaram o papel do estrógeno ou dos ERs na DP e dos polimorfismos genéticos relacionados aos genes NOS e ESR com a condição periodontal. Estudos que avaliassem a presença local e/ou sistêmica dos mediadores inflamatórios que participam do processo da DP com polimorfismos genéticos relacionados seriam interessantes para o processo de avaliação de risco, susceptibilidade e intervenção terapêutica na periodontite.
CONCLUSÕES
Na doença periodontal ocorre maior expressão de IL-10 e iNOS no infiltrado inflamatório, assim como concentrações elevadas de NO e seus metabólitos nos tecidos gengivais, fluido gengival e saliva.
O uso de estrógeno em mulheres na pós-menopausa parece exprimir efeito benéfico na condição periodontal.
Os dados dos estudos avaliados indicam associação dos polimorfismos genéticos no promotor do gene IL 10 com a PAg e com a PC.
Estudos epidemiológicos bem delineados se fazem necessários para validar a relação entre os polimorfismos genéticos no promotor do gene IL 10 e risco à PAg.
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Analysis of genetic polymorphisms in the Interleukin10, NOS2A and ESR2 genes in chronic and aggressive periodontitis
Virginia Régia S. Silveira,* Suzane Cristina Pigossi,†; José Eduardo Tanus dos Santos‡, Raquel Mantuaneli Scarel-Caminaga,† Joni Augusto Cirelli,§ Rodrigo Otávio Rêgo,* Nádia Accioly Pinto Nogueira‖
* Department of Dentistry, School of Dentistry at Sobral, Federal University of Ceará, Sobral, CE, Brazil.
† Department of Morphology, School of Dentistry at Araraquara, UNESP-São Paulo
State University, Araraquara, São Paulo, Brazil.
‡ Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of
São Paulo, Ribeirão Preto, São Paulo, Brazil.
§ Department of Oral Diagnosis and Surgery, School of Dentistry at Araraquara,
UNESP-São Paulo State University, Araraquara, São Paulo, Brazil.
‖ Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Dentistry
and Nursing, Federal University of Ceará, Fortaleza, CE, Brazil.
Correspondence:
Virginia Régia Souza da Silveira, Faculdade de Odontologia, Universidade Federal do Ceará, Campus Sobral, Rua Coronel Estanislau Frota, s/n – CEP 62.010-560, Centro, Sobral, Ceará, Brasil. Tel.:+55-85-9995-0066. e-mail:[email protected]
ABSTRACT
Background: Some genes such as interleukin10 (IL10), inducible nitric oxide synthase 2 (NOS2A) and estrogen receptor (ESR2) play important roles in immune and inflammatory host response and in bone metabolism. The objective of this study was to investigate the association of single nucleotide polymorphisms (SNP) in the IL10, NOS2A and ESR2 genes with chronic periodontitis (CP) and aggressive periodontitis (AgP). Methods: Three groups of patients were evaluated: CP (n=61), AgP (n=50) and periodontally healthy (control group=61). Patients were submitted to periodontal clinical and radiographic examination. Genomic DNA was extracted from oral epithelial cells and utilized for genotyping by polymerase chain reaction in real time (qPCR) using TaqMan® probes. The investigated SNPs were: -1087G>A (rs1800896), -