CRISPLD2 polymorphisms are associated with non‐syndromic cleft lip with or without cleft palate in a northern Chinese population

Abstract

Non-syndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect. This complex genetic disorder results from interactions between genes and environmental factors. Numerous genes have been reported in studies demonstrating association between the cleft lip and palate phenotypes and the alleles at single-nucleotide polymorphisms (SNPs) within specific genes. Recently, the cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) has been revealed to be a novel candidate gene for NSCLP. The SNPs rs1546124, rs4783099 and rs16974880 in CRISPLD2 were highly significant in Caucasian and Hispanic multiplex families but showed no association in Colombian and Irish populations. In the current study, we examined these three SNPs in a northern Chinese population and found an association between these polymorphisms and NSCLP in both single-marker and haplotype analyses. Our data further strengthen the conclusion that altered CRISPLD2 is associated with NSCLP susceptibility.

The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population

“…The genomic region containing CRISPLD2 has been associated with NSCLP in Caucasian and Hispanic populations (Chiquet et al, 2007), a Northern Chinese population (Shi et al 2010) and in an American population (Letra et al, 2010). However, it was suggested that the CRISPLD2 gene did not associate with NSCLP among the Norwegian and Danish populations in Scandinavia (Jugessur et al, 2009), nor in an Irish population in Dublin (Carter et al, 2010), nor in an Italian population (Girardi et al, 2011).…”

“…Shi et al (2010) reported that rs1546124 and rs4783099 were associated with CL/P in a Northern Chinese population (p 5 0.04, p 5 0.03) without Bonferroni multiple adjustments. However, we found that only the CC genotype of rs1546124 was significantly associated with CL/P (p correct 5 1.5 3 10…”

“…In the CPO group, we found rs1546124 to be significantly associated with CPO (p correct 5 5.4 3 10 24 ), and the rs4783099 T polymorphism to have a significant lower risk of CPO (p correct 5 6 3 10 23 ). In contrast, in the Northern Chinese population, only rs4783099 was reported to be associated with CPO (p 5 0.05; Shi et al, 2010). These inconsistencies may be partially owing to heterogeneity of genetic structure and sample capacity between northern and Northwestern Chinese populations.…”

“…Because CL/P and CPO may have different etiologies, patients were stratified to CL/P and CPO groups in which only Shi et al (2010) analyzed in the CRISPLD2 gene. Shi et al (2010) reported that rs1546124 and rs4783099 were associated with CL/P in a Northern Chinese population (p 5 0.04, p 5 0.03) without Bonferroni multiple adjustments.…”

“…However, other association studies yielded conflicting results in different populations (Carter et al, 2010;Girardi et al, 2011;Jugessur et al, 2009;Letra et al, 2010;Shi et al, 2010). It is unclear whether this association crosses ethnic barriers or whether it is anthropologic diversity.…”