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Abstract

Objective

To investigate the association and parental transmission of RUNX2 single nucleotide polymorphisms (SNPs) with risk of nonsyndromic cleft lip with or without cleft palate (NS-CL±P).

Design

Four RUNX2 SNPs in 142 Korean NS-CL±P families (nine cleft lip, 26 cleft lip and alveolus, and 107 cleft lip and palate; 76 trios and 66 dyads) were genotyped. The minor allele frequency, heterozygosity, and chi-square test for Hardy-Weinberg equilibrium at each SNP were computed between parents. Pairwise linkage disequilibrium was computed as D′ and r² for all SNPs. Both allelic and genotypic transmission disequilibrium tests (TDTs) were performed for individual SNPs using a family-based association test program. Sliding windows of haplotypes consisting of two to four SNPs were tested using a haplotype-based association test program. Genotypic odds ratios (GORs) were calculated from conditional logistic regression models. Parent-of-origin effects were assessed using transmission asymmetry test and parent-of-origin likelihood ratio test.

Results

The family-based TDT showed significant evidence of linkage and association at rs1934328 (P = .001). In the haplotype analysis, two, three, and four haplotypes containing rs1934328 revealed significant associations (P = .0017, P = .0022, and P = .0020, respectively). The genotypes A/T and T/T at rs1934328 were significantly associated with NS-CL±P compared with the genotype A/A (GOR = 2.75, 95% confidence interval [CI] = 1.39–5.45, P =0.0019 in the dominant model; GOR = 5.38, 95% CI = 1.34–21.68, P = .0046 in the additive model). However, no parent-of origin effect was observed.

Conclusion

These findings suggest possible involvement of RUNX2-rs 194328 in the etiology of NS-CL±P in Korean cleft-parent trios without excess parental transmission.

Keywords

association nonsyndromic cleft parental transmission RUNX2 SNP

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Investigation of Parental Transmission of RUNX2 Single Nucleotide Polymorphism and Its Association with Nonsyndromic Cleft Lip with or Without Palate

Abstract

Objective

Design

Results

Conclusion

Keywords

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References