Made available in DSpace on 2015-04-14T13:35:32Z (GMT). No. of bitstreams: 1 438286.pdf: 4118090 bytes, checksum: 3f84072ed045d46706a18668827636e2 (MD5) Previous issue date: 2008-11-24 / Introduction: Previous studies showed a possible association between the T102C polymorphism of the serotonin 2A receptor (5-HT2A) and urinary incontinence in the elderly. Since serotonin is involved in the modulation of bladder sphincter control, such association is biologically plausible. Since the pharmacological treatment of urinary incontinence (UI) includes the use of serotonin reuptake inhibitors, complementary studies of this polymorphism are of scientific and clinical importance. Objectives: The aims of this study in older women living in a senior living community were: (1) to describe and compare the allelic and genotypic frequencies of the 102C polymorphism of the serotonin 2A receptor (5-HT2A) in incontinent and continent individuals; (2) to describe and compare the urodynamic parameters in incontinents carrying different genotypes/alleles; (3) to describe and compare the frequency of the urodynamic types of urinary incontinence (stress, urge and mixed) in incontinent individuals carrying different genotypes/alleles; and (4) to describe and compare the impact of UI on the quality of life in incontinent individuals carrying different genotypes/alleles. Methodology: A case-control study was conducted including 68 incontinent older women (submitted to urodynamic evaluation) and 162 continent older women (self-reporting). The criteria for exclusion were: use of diuretics, diabetes, non-Caucasian individuals, and severe mobility and neurological disturbances. The polymorphism was analyzed by the PCR-RFLP technique. The Ethics Committee approved the study, and all participants signed an informed consent form. Results: Incontinent older women showed a significantly greater frequency of the TT genotype (TT= 34.8%, CC= 19.3%, TC= 45.9%) compared to continent older women (TT=17%, CC=23.3%, TC=59.7%) and the general sample of the population (TT=21.5%, CC=16.6%, TC=61.9%) (p=0.001). The genetic frequencies of the three samples were in Hardy-Weinberg equilibrium. Urodynamic analysis showed a significant association between the TT genotype and greater detrusor pressure at maximal cystometric capacity, lower maximal cystometric capacity and reduced bladder compliance. The TT genotype also showed a higher prevalence of urge UI (44%) than did the other genotypes (p=0.01). Analyses of indicators of quality of life and UI demonstrated a greater negative impact in carriers of the C allele (CC+TC). Conclusion: Together, the results suggest that the T102C polymorphism of the 5-HT2A receptor gene has a physiological effect on the lower urinary tract of humans. This hypothesis needs to be confirmed by complementary studies. The effect of an imbalance in the quantity of this receptor, which occurs in the TT genotype, could be associated with a greater chance or urge UI in older women. / Introdu??o: estudos pr?vios mostraram poss?vel associa??o entre o polimorfismo T102C do receptor 2A da serotonina (5-HT2A) e incontin?ncia urin?ria em idosos. Como a serotonina est? envolvida na modula??o do controle vesical-esfincteriano, tal associa??o ? biologicamente plaus?vel. Uma vez que a terap?utica farmacol?gica da incontin?ncia urin?ria (IU) inclui o uso de inibidores da recapta??o da serotonina, estudos complementares deste polimorfismo s?o de relev?ncia cl?nico-cient?fica. Objetivos: em mulheres idosas que vivem na comunidade: (1) descrever e comparar as freq??ncias al?licas e genot?picas do polimorfismo 102C do receptor 2A da serotonina (5-HT2A) em idosas incontinentes e continentes; (2) descrever e comparar os par?metros urodin?micos nas idosas incontinentes portadoras de diferentes gen?tipos/alelos; (3) descrever e comparar a freq??ncia dos tipos de incontin?ncia urin?ria urodin?mica (de esfor?o, de incontin?ncia de urg?ncia e mista) nas idosas incontinentes portadoras de diferentes gen?tipos/alelos; (4) descrever e comparar o impacto da IU na qualidade de vida nas idosas incontinentes portadoras de diferentes gen?tipos/alelos. Metodologia: um estudo caso-controle foi conduzido, sendo 68 mulheres idosas incontinentes (submetidas ? avalia??o urodin?mica) e 162 mulheres continentes (auto-relato). Os crit?rios de exclus?o foram: uso de diur?ticos, diabetes, indiv?duos de outras etnias que n?o a caucasiana, dist?rbios de mobilidade e neurol?gicos graves. O polimorfismo foi analisado por t?cnica de biologia molecular PCR-RFLP. O Comit? de ?tica aprovou a pesquisa e todos os participantes assinaram Termo de Consentimento Livre e Esclarecido. Resultados: idosas incontinentes apresentaram freq??ncia do gen?tipo TT significativamente maior (TT= 34,8%, CC= 19,3%, TC= 45,9%) do que nas mulheres continentes (TT=17%, CC=23,3%, TC=59,7%) e na amostra geral da popula??o (TT=21,5%, CC=16,6%, TC=61,9%) (p=0,001). As freq??ncias gen?ticas das tr?s amostras estavam em equil?brio de Hardy-Weinberg. An?lise urodin?mica mostrou associa??o significativa entre o gen?tipo TT e maior press?o detrusora na capacidade cistom?trica m?xima, menor capacidade cistom?trica m?xima e complac?ncia vesical reduzida. O gen?tipo TT tamb?m apresentou maior preval?ncia de IU de urg?ncia (44%) do que os demais gen?tipos (p=0,01). O conjunto destes resultados sugeriu que o gen?tipo TT est? associado a altera??es de fatores fisiol?gicos, predisponentes a incontin?ncia urin?ria. Entretanto, an?lises de indicadores da qualidade de vida e a IU mostraram maior impacto negativo em portadoras do alelo C (CC+TC). Esta condi??o pode estar associada ? sugest?o de predisposi??o de portadoras do alelo C a dist?rbios emocionais. Conclus?o: o conjunto dos resultados sugere que o polimorfismo T102C do gene do receptor 5-HT2A tenha um poss?vel efeito fisiol?gico no trato urin?rio inferior (TUI) de seres humanos. Esta hip?tese precisa ser confirmada por estudos complementares. O efeito do desbalan?o na quantidade deste receptor, que ocorre no gen?tipo TT estaria associado ? maior chance de IU de urg?ncia na mulher idosa.