Association Studies Between Regulatory Regions of / Genes and Nonsyndromic Oral Clefts.

Objective: To evaluate genetic variants within the regulatory regions of interferon regulatory factor 6 () and for the etiology of nonsyndromic oral clefts risk factors.

Design: We performed allelic transmission disequilibrium test analysis on 5 eligible single-nucleotide polymorphisms (SNPs) and SNP haplotypes using the Family-Based Association Test.

Participants: The study sample consisted of 334 case-parent trios of nonsyndromic oral clefts from Taiwanese population, separated into nonsyndromic cleft lip/palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO) groups.

Results: We found all 3 selected SNPs of the gene show significant association with nonsyndromic oral clefts (rs2235371, = 5.10E-07; rs642961, = .00194; and rs77542756, = 9.08E-07). Haplotype analyses identified 3 possible SNP combination haplotypes in the gene and found that C-G-G showed significant undertransmission ( = .058), whereas 2 other haplotypes, T-G-A and C-A-G ( = 2.71E-06 and = 5.00E-04, respectively), were significantly overtransmitted to the NSCL/P children but not to the NSCPO children. For the gene, we failed to detect evidence of nonsyndromic oral cleft association in the 2 SNPs within the large intron 1 region.

Conclusions: We used a family-based analysis in 334 Taiwanese case-parent trios to evaluate selected SNPs of genes and genes for a risk of orofacial clefting. This study provides additional evidence for an association between and NSCL/P, including the genetic variants within the 5'-noncoding region of the gene. We also confirmed that NSCL/P and NSCPO individuals belong to different groups. For the TP63, our data did not favor the direct involvement of TAp63 isoforms during orofacial development.