Study of the association between the BMP4 gene and congenital anomalies of the kidney and urinary tract

Reis, Geisilaine Soares dos; Silva, Ana Cristina Simões e; Freitas, Izabella Silva; Heilbuth, Thiago Ramos; Marco, Luiz Armando de; Oliveira, Eduardo Araújo; Miranda, Débora Marques

doi:10.1016/j.jpedp.2013.06.003

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Abstract

Objective

To determine the frequency of different phenotypes for congenital anomalies of the kidney and urinary tract (CAKUT) in a Brazilian sample, and to evaluate the association between the CAKUT phenotypes and the BMP4 gene.

Methods

In this study, 457 Brazilian individuals were analyzed in an attempt to establish the association between the BMP4 gene and the CAKUT diagnosis. A case-control sample was genotyped for three BMP4 gene polymorphisms.

Results

Association data was established with CAKUT sample as a whole and with the three most important CAKUT phenotypes: multicystic dysplastic kidney disease (MDK), ureteropelvic junction obstruction (UPJO) and vesicoureteral reflux (VUR). When the sample was segregated in these three phenotypes, associations between the BMP4 gene were observed with UPJO and with MDK. Conversely, VUR was not associated to the polymorphisms of the BMP4 gene.

Conclusions

The present data suggest that Brazilian individuals with polymorphisms of the BMP4 gene have a higher risk to develop CAKUT, especially the malformations related to nephrogenesis and initial branching such as MDK and UPJO. Conversely, VUR appeared not to be related to BMP4 gene.

Keywords:

Association study

BMP4

Congenital anomalies of the kidney and urinary tract

CAKUT

Resumo

Objetivo

: Determinar a frequência de diferentes fenótipos de anomalias congênitas do rim e trato urinário (CAKUT) em uma amostra brasileira e avaliar a associação entre os CAKUT e o gene BMP-4.

Métodos

Neste estudo, analisamos 457 indivíduos brasileiros em uma tentativa de esta- belecera associação entre o gene BMP-4 e o diagnóstico de CAKUT. As amostras de caso e de controle foram genotipadas em busca de três polimorfismos do gene BMP-4.

Resultados

Os dados de associação foram estabelecidos com a amostra de CAKUT como um todo e com os três fenótipos de CAKUT mais importantes: rim displásico multicístico (RDM), obstrução da junção ureteropélvica (UPJO) e refluxo vesico-ureteral (VUR). Quan- do a amostra foi separada nesses três fenótipos, encontramos associações entre o gene BMP-4 com UPJO e com RDM. Por outro lado, o VUR não foi associado aos polimorfismos do gene BMP-4.

Conclusões

Esses dados sugerem que os indivíduos brasileiros com polimorfismos do gene BMP-4 apresentam maior risco de desenvolver CAKUT, principalmente as malfor- mações relacionadas a nefrogênese e ramificação inicial, como RDM e UPJO. Por outro lado, o VUR parece não estar relacionado ao gene BMP-4.

Palavras-chave:

Estudo de associação

BMP-4

Anomalias congênitas do rim e do trato urinário

CAKUT

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☆

Como citar este artigo: Reis GS, Simões e Silva AC, Freitas IS, Heilbuth TR, Marco LA, Oliveira EA, et al. Study of the association bet-ween the BMP4 gene and congenital anomalies of the kidney and urinary tract. J Pediatr (Rio J). 2014;90:58-64.

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