Contribution of 6p24 to non-syndromic cleft lip and palate in a Malay population: association of variants in OFC1

Non-syndromic cleft lip, with or without cleft palate, is a heterogeneous, complex disease with a high incidence in the Asian population. Several association studies have been done on cleft candidate genes, but no reports have been published thus far on the Orofacial Cleft 1 (OFC1) genomic region in an Asian population. This study investigated the association between the OFC1 genomic region and non-syndromic cleft lip with or without cleft palate in 90 Malay father-mother-offspring trios. Results showed a preferential over-transmission of a 101-bp allele of marker D6S470 in the allele- and haplotype-based transmission disequilibrium test (TDT), as well as an excess of maternal transmission. However, no significant p-value was found for a maternal genotype effect in a log-linear model, although single and double doses of the 101-bp allele showed a slightly increased cleft risk (RR = 1.37, 95% CI, 0.527-3.4, p-value = 0.516). Carrying two copies of the 101-bp allele was significantly associated with an increased cleft risk (RR = 2.53, 95% CI, 1.06-6.12, p-value = 0.035). In conclusion, we report evidence of the contribution of the OFC1 genomic region to the etiology of clefts in a Malay population.