Ana Camila Messetti1, Renato Assis Machado1, Carine Ervolino de Oliveira1, Hercílio Martelli-Júnior2,3, Silvia Regina de Almeida Reis4, Helenara Salvati Bertolossi Moreira5, Darlene Camati Persuhn6, Tao Wu7, Ricardo D Coletta1. 1. Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil. 2. Stomatology Clinic, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil. 3. Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of José Rosario Vellano, Alfenas, Minas Gerais, Brazil. 4. Department of Basic Science, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil. 5. Department of Physiotherapy, State University of Western Paraná, Cascavel, Paraná, Brazil. 6. Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 7. Peking University School of Public Health, Beijing, China.
Abstract
BACKGROUND: Variants in the cysteine-rich secretory protein LCCL domain containing 2 gene (CRISPLD2) and in the jumonji, AT-rich interaction domain 2 gene (JARID2) were previously shown to influence non-syndromic oral cleft susceptibility. Herein, we performed a case-control study to examine the potential association of single-nucleotide polymorphisms (SNPs) in CRISPLD2 and JARID2 with non-syndromic cleft lip and/or palate (NSCL/P) in the Brazilian population. Given the ethnicity-dependent genetic predisposition to NSCL/P, we performed a structured analysis taking into account the genomic ancestry variation of each individual. METHODS: Four SNPs in CRISPLD2 (rs1546124, rs8061351, rs2326398, and rs4783099) and four in JARID2 (rs915344, rs2299043, rs2237138, and rs2076056), that were previously reported to be associated with NSCL/P, were genotyped in 785 Brazilian patients with NSCL/P (549 with cleft lip with or without cleft palate-NSCL ± P, and 236 with cleft palate only-NSCPO) and 693 unaffected Brazilian controls. Genomic ancestry was assessed with a set of 40 biallelic short insertion/deletion variants previously validated as ancestry informative markers of the Brazilian population. RESULTS: After adjustment of ancestry variations, allelic analysis revealed marginal associations between the CRISPLD2 rs4783099 T allele and increased risk for NSCPO (OR: 1.31, 95% CI: 1.05-1.62, P = 0.01) and between JARID2 rs2237138 and decreased NSCL ± P risk (OR: 0.80, 95% CI: 0.67-0.97, P = 0.02). Haplotype analysis indicated a lack of association between JARID2 haplotypes and non-syndromic oral cleft risk. CONCLUSIONS: Our results suggest that CRISPLD2 rs4783099 may represent a risk factor for NSCPO while JARID2 rs2237138 shows a protective effect against NSCL ± P in the Brazilian population.
BACKGROUND: Variants in the cysteine-rich secretory protein LCCL domain containing 2 gene (CRISPLD2) and in the jumonji, AT-rich interaction domain 2 gene (JARID2) were previously shown to influence non-syndromic oral cleft susceptibility. Herein, we performed a case-control study to examine the potential association of single-nucleotide polymorphisms (SNPs) in CRISPLD2 and JARID2 with non-syndromic cleft lip and/or palate (NSCL/P) in the Brazilian population. Given the ethnicity-dependent genetic predisposition to NSCL/P, we performed a structured analysis taking into account the genomic ancestry variation of each individual. METHODS: Four SNPs in CRISPLD2 (rs1546124, rs8061351, rs2326398, and rs4783099) and four in JARID2 (rs915344, rs2299043, rs2237138, and rs2076056), that were previously reported to be associated with NSCL/P, were genotyped in 785 Brazilian patients with NSCL/P (549 with cleft lip with or without cleft palate-NSCL ± P, and 236 with cleft palate only-NSCPO) and 693 unaffected Brazilian controls. Genomic ancestry was assessed with a set of 40 biallelic short insertion/deletion variants previously validated as ancestry informative markers of the Brazilian population. RESULTS: After adjustment of ancestry variations, allelic analysis revealed marginal associations between the CRISPLD2rs4783099 T allele and increased risk for NSCPO (OR: 1.31, 95% CI: 1.05-1.62, P = 0.01) and between JARID2rs2237138 and decreased NSCL ± P risk (OR: 0.80, 95% CI: 0.67-0.97, P = 0.02). Haplotype analysis indicated a lack of association between JARID2 haplotypes and non-syndromic oral cleft risk. CONCLUSIONS: Our results suggest that CRISPLD2rs4783099 may represent a risk factor for NSCPO while JARID2rs2237138 shows a protective effect against NSCL ± P in the Brazilian population.
Authors: Eline A Verberne; Shuxiang Goh; Jade England; Mieke M van Haelst; Philippe M Campeau; Manon van Ginkel; Louise Rafael-Croes; Saskia Maas; Abeltje Polstra; Yuri A Zarate; Katherine A Bosanko; Kieran B Pechter; Emma Bedoukian; Kosuke Izumi; Ayeshah Chaudhry; Nathaniel H Robin; Megan Boothe; Natalie C Lippa; Vimla Aggarwal; Darryl C De Vivo; Anna Lehman; Causes Study; Sylvia Stockler; Ange-Line Bruel; Bertrand Isidor; Jennifer Lemons; David F Rodriguez-Buritica; Christopher M Richmond; Zornitza Stark; Pankaj B Agrawal; R Frank Kooy; Marije E C Meuwissen; David A Koolen; Rolf Pfundt; Agne Lieden; Britt-Marie Anderlid; Dagmar Glatz; Marcel M A M Mannens; Madhura Bakshi; Frédérick A Mallette Journal: Genet Med Date: 2020-10-20 Impact factor: 8.822
Authors: Renato Assis Machado; Hercílio Martelli-Junior; Silvia Regina de Almeida Reis; Erika Calvano Küchler; Rafaela Scariot; Lucimara Teixeira das Neves; Ricardo D Coletta Journal: Front Cell Dev Biol Date: 2021-07-08