Tânia Kawasaki de Araujo1, Rodrigo Secolin1, Têmis Maria Félix2, Liliane Todeschini de Souza2, Marshall Ítalo Barros Fontes3, Isabella Lopes Monlleó4, Josiane de Souza5, Agnes Cristina Fett-Conte6, Erlane Marques Ribeiro7, Ana Carolina Xavier8, Adriana Augusto de Rezende9, Milena Simioni1, Ândrea Kely Campos Ribeiro-dos-Santos10, Sidney Emanuel Batista dos Santos10, Vera Lúcia Gil-da-Silva-Lopes11. 1. Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil. 2. Medical Genetics Service, Hospital de Clinicas de Porto Alegre, 90035-903 Porto Alegre, RS, Brazil. 3. Medical Genetics Sector, State University of Alagoas (UNCISAL), 57010-300 Maceió, AL, Brazil. 4. Clinical Genetics Service, Faculty of Medicine, University Hospital, Federal University of Alagoas (UFAL), 57072-970 Maceió, AL, Brazil. 5. Centro de Atendimento Integral ao Fissurado Labiopalatal (CAIF), 81050-00 Curitiba, PR, Brazil. 6. Department of Molecular Biology, Medical School in São José do Rio Preto (FAMERP FUNFARME), 15090-000 São José do Rio Preto, SP, Brazil. 7. Medical Genetics Service, Hospital Infantil Albert Sabin - HIAS, 60410-790 Fortaleza, CE, Brazil. 8. Center for Research and Rehabilitation of Lip and Palate Lesions (CRRLPL), Centrinho Prefeito Luiz Gomes, 89203-020 Joinville, SC, Brazil. 9. Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Hospital Onofre Lopes (HUOL), Federal University of Rio Grande do Norte (UFRN), 59012-570 Natal, RN, Brazil. 10. Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, 66.075-970 PA, Brazil. 11. Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil. Electronic address: vlopes@fcm.unicamp.br.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Authors: Kurt Reynolds; Shuwen Zhang; Bo Sun; Michael A Garland; Yu Ji; Chengji J Zhou Journal: Birth Defects Res Date: 2020-07-15 Impact factor: 2.344
Authors: W Y Li; M Y Wang; R Zhou; S Y Wang; H C Zheng; H P Zhu; Z B Zhou; T Wu; H Wang; B Shi Journal: Beijing Da Xue Xue Bao Yi Xue Ban Date: 2020-10-18
Authors: Azeez Butali; Peter A Mossey; Wasiu L Adeyemo; Mekonen A Eshete; Lord J J Gowans; Tamara D Busch; Deepti Jain; Wenjie Yu; Liu Huan; Cecelia A Laurie; Cathy C Laurie; Sarah Nelson; Mary Li; Pedro A Sanchez-Lara; William P Magee; Kathleen S Magee; Allyn Auslander; Frederick Brindopke; Denise M Kay; Michele Caggana; Paul A Romitti; James L Mills; Rosemary Audu; Chika Onwuamah; Ganiyu O Oseni; Arwa Owais; Olutayo James; Peter B Olaitan; Babatunde S Aregbesola; Ramat O Braimah; Fadekemi O Oginni; Ayodeji O Oladele; Saidu A Bello; Jennifer Rhodes; Rita Shiang; Peter Donkor; Solomon Obiri-Yeboah; Fareed Kow Nanse Arthur; Peter Twumasi; Pius Agbenorku; Gyikua Plange-Rhule; Alexander Acheampong Oti; Olugbenga M Ogunlewe; Afisu A Oladega; Adegbayi A Adekunle; Akinwunmi O Erinoso; Olatunbosun O Adamson; Abosede A Elufowoju; Oluwanifemi I Ayelomi; Taiye Hailu; Abiye Hailu; Yohannes Demissie; Miliard Derebew; Steve Eliason; Miguel Romero-Bustillous; Cynthia Lo; James Park; Shaan Desai; Muiawa Mohammed; Firke Abate; Lukman O Abdur-Rahman; Deepti Anand; Irfaan Saadi; Abimibola V Oladugba; Salil A Lachke; Brad A Amendt; Charles N Rotimi; Mary L Marazita; Robert A Cornell; Jeffrey C Murray; Adebowale A Adeyemo Journal: Hum Mol Genet Date: 2019-03-15 Impact factor: 6.150
Authors: Raquel M Scarel-Caminaga; Flávia F Cera; Suzane C Pigossi; Livia S Finoti; Yeon J Kim; Aline C Viana; Rodrigo Secolin; Marcelo F Montenegro; José E Tanus-Santos; Silvana R P Orrico; Joni A Cirelli Journal: Int J Mol Sci Date: 2017-06-15 Impact factor: 5.923
Authors: L J J Gowans; W L Adeyemo; M Eshete; P A Mossey; T Busch; B Aregbesola; P Donkor; F K N Arthur; S A Bello; A Martinez; M Li; E A Augustine-Akpan; W Deressa; P Twumasi; J Olutayo; M Deribew; P Agbenorku; A A Oti; R Braimah; G Plange-Rhule; M Gesses; S Obiri-Yeboah; G O Oseni; P B Olaitan; L Abdur-Rahman; F Abate; T Hailu; P Gravem; M O Ogunlewe; C J Buxó; M L Marazita; A A Adeyemo; J C Murray; A Butali Journal: J Dent Res Date: 2016-07-01 Impact factor: 8.924