Transforming Growth Factor-β3 Gene SfaN1 Polymorphism in Korean Nonsyndromic Cleft Lip and Palate Patients
Authors
Myung-Hee Kim†, Hyo-Jin Kim‡, Je-Yong Choi‡,* and Dong-Seok Nahm†,*
Institutions
†Department of Orthodontics, College of Dentistry, Seoul National University, Seoul 110-744, Korea , ‡Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu 700-422, Korea
Abstract
The nonsyndromic cleft lip and palate (NSCL/P) is a congenital deformity of multifactorial origin with a relatively high incidence in the oriental population. Various etiologic candidate genes have been reported with conflicting results, according to race and analysis methods. Recently, the ablation of the TGF-β3 gene function induced cleft palates in experimental animals. Also, polymorphisms in the TGF-β3 gene have been studied in different races; however, they have not been studied in Koreans. A novel A → G single nucleotide polymorphism (defined by the endonuclease SfaN1) was identified in intron 5 of TGF-β3 (IVS5+104 A > G). It resulted in different genotypes, AA, AG, and GG. The objective of this study was to investigate the relationship between the SfaN1 polymorphism in TGF-β3 and the risk of NSCL/P in the Korean population. The population of this study consisted of 28 NSCL/P patients and 41 healthy controls. The distribution of the SfaN1 genotypes was different between the cases and controls. The frequency of the G allele was significantly associated with the increased risk of NSCL/P [odds ratio (OR) = 15.92, 95% confidence interval (CI) = 6.3-41.0]. The risk for the disease increased as the G allele numbers increased (GA genotype: OR = 2.11, 95% CI = 0.38-11.68; GG genotype: OR = 110.2, 95% CI = 10.67 - 2783.29) in NSCL/P. A stratified study in patients revealed that the SfaN1 site IVS5+104A > G substitution was strongly associated with an increased risk of NSCL/P in males (p < 0.001), but not in females. In conclusion, the polymorphism of the SfaN1 site in TGF-β3 was significantly different between the NSCL/P patients and the control. This may be a good screening marker for NSCL/P patients among Koreans.
