Dataset Information

CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate.

ABSTRACT: OBJECTIVE:To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2). DESIGN:Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351, rs2326398, rs4783099) were genotyped to test for association via family-based association methods. PARTICIPANTS:A total of 5826 individuals from 1331 families in which one or more family member is affected with CL(P). RESULTS:Evidence of association was seen for SNP rs1546124 in U.S. (p ?=? .02) and Brazilian (p ?=? .04) Caucasian cohorts. We also found association of SNP rs1546124 with cleft palate alone (CP) in South Americans (Guatemala and ECLAMC) and combined Hispanics (Guatemala, ECLAMC, and Texas Hispanics; p ?=? .03 for both comparisons) and with both cleft lip with cleft palate (CLP; p ?=? .04) and CL(P) (p ?=? .02) in North Americans. Strong evidence of association was found for SNP rs2326398 with CP in Asian populations (p ?=? .003) and with CL(P) in Hispanics (p ?=? .03) and also with bilateral CL(P) in Brazilians (p ?=? .004). In Brazilians, SNP rs8061351 showed association with cleft subgroups incomplete CL(P) (p ?=? .004) and unilateral incomplete CL(P) (p ?=? .003). Prediction of SNP functionality revealed that the C allele in the C471T silent mutation (overrepresented in cases with CL(P) presents two putative exonic splicing enhancer motifs and creates a binding site AP-2 alpha, a transcription factor involved in craniofacial development. CONCLUSIONS:Our results support the hypothesis that variants in the CRISPLD2 gene may be involved in the etiology of NS CL(P).

SUBMITTER: Letra A

PROVIDER: S-EPMC3000893 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate.

Letra Ariadne A Menezes Renato R Cooper Margaret E ME Fonseca Renata F RF Tropp Stephen S Govil Manika M Granjeiro Jose M JM Imoehl Sandra R SR Mansilla M Adela MA Murray Jeffrey C JC Castilla Eduardo E EE Orioli Iêda M IM Czeizel Andrew E AE Ma Lian L Chiquet Brett T BT Hecht Jacqueline T JT Vieira Alexandre R AR Marazita Mary L ML

The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 20100701 4

<h4>Objective</h4>To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2).<h4>Design</h4>Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351, rs2326398, rs4783099) were genotyped to test for association via family-based association methods.<h4>Participants</h4>A total of 5826 individuals from 1331 families in which o ...[more]

PMID: 20815724

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Project description:BackgroundPrevious studies have investigated the relationship between human bone morphogenetic protein 4 gene (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, the results remained inconsistent. Therefore, we conducted a meta-analysis to assess the effect of BMP4 rs17563 polymorphism on NSCL/P.MethodsElectronic searches in 5 databases were conducted to select all eligible studies up to March 2017. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated to estimate the association. Sensitivity analysis was performed to evaluate the results stability by excluding each study in turn. Publication bias was assessed by Begg funnel plots and Egger test.ResultsA total of 11 case-control studies were included in the meta-analysis. The pooled frequency of the minor allele C for BMP4 rs17563 was lower in Asians (pooled frequency = 0.33, 95% CI: 0.29-0.37) than in Brazilian population (pooled frequency = 0.47, 95% CI: 0.40-0.54). The overall results showed no significant association of BMP4 rs17563 polymorphism with NSCL/P risk. However, the results turned out to be different when stratified by ethnicity. BMP4 rs17563 polymorphism was associated with a higher risk of NSCL/P among Asian ethnicity (C vs T: OR = 1.33, 95% CI: 1.02-1.73; CC vs TT: OR = 2.10, 95% CI: 1.28-3.43; CC vs TT + TC: OR = 2.16, 95% CI: 1.34-3.47) and among Caucasian population (TC vs TT: OR = 3.36, 95% CI: 2.03-5.54; TC + CC vs TT: OR = 3.71, 95% CI: 2.43-5.69). Among Brazilian population, BMP4 rs17563 polymorphism exerted a significantly protective effect on NSCL/P (C vs T: OR = 0.70, 95% CI: 0.58-0.84; CC vs TT: OR = 0.54, 95% CI: 0.33-0.88; TC vs TT: OR = 0.55, 95% CI: 0.44-0.69; TC + CC vs TT: OR = 0.56, 95% CI: 0.45-0.69).ConclusionThe results suggest that the C allele of BMP4 rs17563 may be a risk factor for NSCL/P among Asians and Caucasians, and may be a protective factor for NSCL/P in Brazilian population. Future large-sample studies with appropriate designs among specific populations are warranted to evaluate the association.

Dataset Information

CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate.

Publications

CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate.

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