MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate

Abstract

Recent studies suggest that multiple interacting loci, with possible additional environmental factors, influence the risk for nonsyndromic oral clefts, one of the most common birth defects in humans. Advances in high-throughput genotyping technology allow the testing of multiple markers, simultaneously, in many candidate genes. We tested for associations between 176 haplotype-tagging single nucleotide polymorphisms (SNPs) in 18 candidate genes/loci and nonsyndromic clefts in a case-control study in an Estonian sample (153 patients, 205 controls). The most significant associations with nonsyndromic cleft lip with or without cleft palate (CL/P) were found for SNPs in MSX1, MTHFR, and PVRL2, including several common haplotypes in the MTHFR and MSX1 genes. The strongest association was observed for rs6446693 in the MSX1 region, which remained statistically significant after Bonferroni correction. The strongest association with nonsyndromic cleft palate (CP) was found for the SNP rs11624283 in the JAG2 gene. Epistatic interactions were observed for SNPs within PVRL2, between BCL3 and EDN1, and between IRF6 and MSX1 genes. This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations.

Association of TGFB3 rs2300607 (IVSI+ 5321) Gene Variant with Non Syndromic Cleft Lip/Palate in South Indian Patients

“…In this study 40% of the cases having non syndromal cleft lip/palate did not show any of these gene variants .This may suggest the possibility of involvement of other genes as non syndromal cleft lip/palate is of polygentic nature and studies suggest that other genes like TGFB3, RARA, BCLX3, TGFαA, MTHR, PVLRI [1,14] are involved in the etiology of non syndromal cleft lip/palate.…”

Coding Regions of MSX1 do not Contribute to Non-Syndromic Cleft Lip With/Without Palate in Turkish Patients

“…According to the previous studies, mutations in MSX1 can contribute to NSCL/P as many as 2% of the total cases [10,11]. Some studies reported the mutations and/or polymorphisms do not contribute to the anomaly in the examined populations [12,13], and some others reported the variations contribute to the anomaly [14,15]. The unrepeated results from different populations with different ethnicity showed the variability nature of MSX1 for the onset of NS-CL/P.…”

Genetic Aspects of Cleft Lip and Palate ? A Review

“…The chief function of EDN 1 is considered to be the maintenance of the vascular tone. There are few studies that have showed the mutant EDN 1 genes can result in isolated CP [31].…”