Brazilian multicenter study of association between polymorphisms in CRISPLD2 and JARID2 and non-syndromic oral clefts.
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.
Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Ana Camila
AC
Messetti
Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Renato Assis
RA
Machado
Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Carine Ervolino
CE
de Oliveira
Stomatology Clinic, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil.|Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of José Rosario Vellano, Alfenas, Minas Gerais, Brazil.
Hercílio
H
Martelli-Júnior
Department of Basic Science, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil.
Silvia Regina
SR
de Almeida Reis
Department of Physiotherapy, State University of Western Paraná, Cascavel, Paraná, Brazil.
Helenara Salvati Bertolossi
HS
Moreira
Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.
Darlene Camati
DC
Persuhn
Peking University School of Public Health, Beijing, China.
Tao
T
Wu
Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Ricardo D
RD
Coletta
D000328:Adult; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C525599:CRISPLD2 protein, human; D015815:Cell Adhesion Molecules; D050835:Interferon Regulatory Factors; C547777:JARID2 protein, human; D063151:Polycomb Repressive Complex 2
CRISPLD2; JARID2; cleft lip and/or palate; single-nucleotide polymorphism