A multicentric association study between 39 genes and nonsyndromic cleft lip and palate in a Brazilian population

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• 作者：Tâ ; nia Kawasaki de Araujo^a ; Rodrigo Secolin^a ; Tê ; mis Maria Fé ; lix^b ; Liliane Todeschini de Souza^b ; Marshall Í ; talo Barros Fontes^c ; Isabella Lopes Monlleó ; ^d ; Josiane de Souza^e ; Agnes Cristina Fett-Conte^f ; Erlane Marques Ribeiro^g ; Ana Carolina Xavier^h ; Adriana Augusto de Rezendeⁱ ; Milena Simioni^a ; Â ; ndrea Kely Campos Ribeiro-dos-Santos^j ; Sidney Emanuel Batista dos Santos^j ; Vera Lú ; cia Gil-da-Silva-Lopes^a ; ^{vlopes@fcm.unicamp.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nonsyndromic cleft lip and cleft palate ; Case-control association study ; Single nucleotide polymorphism ; KIF7 ; TCEB3
• 刊名：Journal of Cranio-Maxillofacial Surgery
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：44
• 期：1
• 页码：16-20
• 全文大小：596 K

文摘

The aim of this study was to use the TaqMan OpenArray system to evaluate associations between 39 genes and the etiology of nonsyndromic cleft lip and palate (NSCLP) in a Brazilian population.

Material and methods

This case-control association study was designed with 80.11% statistical power according to logistic regression (GPOWER software). The case group had 182 patients with NSCLP enrolled in the Brazilian Database on Orofacial Clefts. The controls included 355 healthy individuals with no history of oral clefting in the past three generations. All samples were genotyped for 253 tag single nucleotide polymorphisms (tagSNPs) in 39 genes, including two that had recently been associated with this process. The association analysis was performed using logistic regression and stepwise regression. The results were corrected for multiple testing [Bonferroni correction and False Discovery Rate (FDR)].

Results

Twenty-four SNPs in 16 genes were significantly associated with the etiology of NSCLP, including MSX1, SPRY1, MSX2, PRSS35, TFAP2A, SHH, VAX1, TBX10, WNT11, PAX9, BMP4, JAG2, AXIN2, DVL2, KIF7, and TCBE3. Stepwise regression analysis revealed that 11 genes contributed to 15.5% of the etiology of NSCLP in the sample.

Conclusion

This is the first study to associate KIF7 and TCEB3 with the etiology of NSCLP. New technological approaches using the same design should help to identify further etiological susceptibility variants.