[Transmission disequilibrium test for nonsyndromic cleft lip and palate and segment homeobox gene-1 gene].

OBJECTIVE: To investigate the relationship between muscle segment homeobox gene-1 (MSX1) and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. METHODS: One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic marker. The genotypes of 387 members in 129 NSCLP nuclear family trios were analyzed by polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test (TDT) and Logistic regression analysis were used to conduct association analysis. RESULTS: TDT analysis confirmed that CA4 allele in CL/P and CPO groups preferentially transmitted to the affected offspring (P = 0.018, P = 0.041). Logistic regression analysis indicated that the recessive model of inheritance was supported, and CA4 itself or CA4 acting as a marker for a disease allele or haplotype was inherited in a recessive fashion (P = 0.009). CONCLUSIONS: MSX1 gene is associated with NSCLP, and MSX1 gene may be directly involved either in the etiology of NSCLP or in linkage disequilibrium with disease-predisposing sites.

[Association study on microsatellite polymorphisms of MSX1 gene and nonsyndromic cleft lip and palate].

OBJECTIVE: To investigate muscle segment homeobox 1 (MSX1) microsatellite marker distribution and the relationship between MSX1 gene and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. METHODS: One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic markers. The genotypes of 129 patients with NSCLP and 108 controls were analyzed by the techniques of polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis (PAGE). Then case-control study was used to conduct association analysis. RESULTS: The allele frequencies of the CA repeat microsatellite DNA in Hunan Han normal population were in good agreement with Hardy-Weinberg equilibrium. The polymorphism information content and heterozygosity of CA repeat microsatellite DNA were 0.50 and 0.50 respectively. The allele CA4 frequency in CL/P and CPO group was significantly higher than that of normal controls (P<0.05). The genotype CA4,4 frequency was significantly higher in CL/P and CPO group than that in normal controls (P<0.05). CONCLUSION: The microsatellite DNA marker CA repeat in MSX1 is a good genetic marker. MSX1 gene is significantly associated with NSCLP in Hunan Hans.

[Association between retinoic acid receptor alpha gene polymorphisms and nonsyndromic cleft lip with or without cleft palate susceptibility].

OBJECTIVE: To investigate the relationship between D17S579 microsatellite marker allelic polymorphisms in retinoic acid receptor-alpha (RARA) gene and the genetic susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Hunan Hans. METHODS: PCR and denaturing polyacrylamide gel electrophoresis (PAGE) were used to detect the polymorphism of RARA gene marked by D17S579 among 140 patients with NSCL/P, 82 males and 58 females, aged 3 months-14 years, and 132 healthy persons, 68 males and 64 females, aged 6 months-14 years, who underwent physical examination. RESULTS: The A6 allele frequency of the NSCL/P patients was 8.93%, significantly higher than that of the healthy persons (4.17%, P = 0.026). The A9 allele frequency the NSCL/P patients was 13.21%, significantly higher than that of the healthy persons (5.68%, P = 0.003). There were not significant differences in the frequencies of different alleles between the patients with family history and the patients without family history (chi2 = 2.710, P = 0.978). CONCLUSION: The A6 and A9 alleles in D17S579 microsatellite marker of RARA gene may be correlated with the development of NSCL/P in Hunan Hans. There is no association between the family history and RARA polymorphism in the NSCL/P patients.