Rahimov et al. (2008) found that the A allele of a common SNP (dbSNP rs642961, G-A) in an IRF6 enhancer within the 5-prime untranslated region of the IRF6 gene was significantly overtransmitted (p = 1 x 10(-11)) in ... Rahimov et al. (2008) found that the A allele of a common SNP (dbSNP rs642961, G-A) in an IRF6 enhancer within the 5-prime untranslated region of the IRF6 gene was significantly overtransmitted (p = 1 x 10(-11)) in families with nonsyndromic cleft lip/palate, particularly in those with cleft lip only. There was a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. In a hospital-based case-control study of 134 Han Chinese patients with nonsyndromic orofacial clefting (NSOC) and 115 controls matched for age, sex, and residential area, Pan et al. (2010) genotyped 2 polymorphisms in the IRF6 gene, dbSNP rs2235371 and dbSNP rs642961. In single-locus analyses, they found that the dbSNP rs642961 AG and AG/AA genotypes were associated with increased risk of NSOC, especially cleft lip with or without cleft palate (CL/P) and cleft lip with cleft palate (CLP), whereas significantly decreased risks were associated with dbSNP rs2235371 CT and CT/TT genotypes. In combined analysis using the dbSNP rs642961 A allele and the dbSNP rs2235371 C allele as the risk alleles, Pan et al. (2010) found that genotypes containing 2 to 4 risk alleles conferred high risk for NSOC, CL/P, and CLP (odds ratios of 2.15, 2.06, and 2.66, respectively). Analysis of lip skin tissue adjacent to the cleft revealed that dbSNP rs642961 genotypes were associated with differential levels of IRF6 mRNA and protein expression in an allele-dosage manner. Pan et al. (2010) concluded that IRF6 genetic variants contribute to the etiology of NSOC in the Han Chinese population.