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Document Type

Article

Abstract

Prior studies have implicated an involvement of the Msxl homeobox gene in cleft palate in mice and its homolog in humans (called MSXI in the HOX7 gene, located on chromosome 4), In this study we present evidence of a sex-dependent association between MSXl and nonsyndromic cleft lip/palate (NSCLP) in the Chilean population. The sample included 73 NSCLP cases, 37 from multiplex families (Mx), 36 from simplex families (Sx), and 87 controls. Polymerase chain reaction amplification of the MSXl intragenic microsatellite (CA)n-sequence shows significant (1' = 0.035) differences in the allele frequencies between NSCLP-Mx males and control males. These differences are mainly due to frequency differences in allele *2 (173 base pairs) among cases (21.9%) and controls (13.2%). When the NSCLP cases are subdivided by sex and positive family history (Mx versus Sx), the Mx males (27.8%) as well as the total NSCLP-Mx cases (25.7%) showed significantly higher frequencies of allele *2, compared to controls (11.4% and 13.2%, respectively). Analysis of the genotype data indicates that the relative risk for NSCLP is greater for persons calTying allele *2 (i.e., odds ratio [OR] larger than 1), reaching significance for all Mx cases (OR = 2.67; 95% confidence interval [CI], 1.10 to 6.52) and even more pronounced for Mx males (OR = 3.33: 95% CI, 1.08 to 10.32). Taken together, these findings support the hypothesis that the genetic variation at the MSXI locus is a predisposing gene involved in sex-dependent susceptibility to c1efting and that it also differentiates simplex from mUltiplex families.

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