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Brazilian multicenter study of association between polymorphisms in CRISPLD 2 and JARID 2 and non‐syndromic oral clefts
Author(s) -
Messetti Ana Camila,
Machado Renato Assis,
Oliveira Carine Ervolino,
MartelliJúnior Hercílio,
Almeida Reis Silvia Regina,
Moreira Helenara Salvati Bertolossi,
Persuhn Darlene Camati,
Wu Tao,
Coletta Ricardo D.
Publication year - 2017
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12470
Subject(s) - multicenter study , medicine , genetics , biology , randomized controlled trial
Background Variants in the cysteine‐rich secretory protein LCCL domain containing 2 gene ( CRISPLD 2 ) and in the jumonji, AT ‐rich interaction domain 2 gene ( JARID 2 ) 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 ( SNP s) in CRISPLD 2 and JARID 2 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 SNP s in CRISPLD 2 (rs1546124, rs8061351, rs2326398, and rs4783099) and four in JARID 2 (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 CRISPLD 2 rs4783099 T allele and increased risk for NSCPO ( OR : 1.31, 95% CI : 1.05–1.62, P = 0.01) and between JARID 2 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 JARID 2 haplotypes and non‐syndromic oral cleft risk. Conclusions Our results suggest that CRISPLD 2 rs4783099 may represent a risk factor for NSCPO while JARID 2 rs2237138 shows a protective effect against NSCL ± P in the Brazilian population.